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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 V ariation i n Recovery: R ole of G ender on O utcomes 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., (© 2022 The Authors.)

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., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: Competing interests: RPD reports research funding from the American Heart Association, the Canadian Institutes of Health Research and from the Medical Device Innovation Consortium (MDIC) as part of the National Evaluation System for health Technology Coordinating Center (NESTcc), Food and Drug Administration (FDA). JSR received research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from the FDA to establish the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation (CERSI) program (U01FD005938), MDIC as part of the NESTcc, AHRQ (R01HS022882), NHLBI of the NIH (R01HS025164, R01HL144644), and from the Laura and John Arnold Foundation to establish the Good Pharma Scorecard at Bioethics International and to establish the Collaboration for Research Integrity and Transparency (CRIT) at Yale. NDS is currently employed by Delta Airlines; when he was employed by the Mayo Clinic, he reported receiving research support through Mayo Clinic from the Food and Drug Administration, the Centers of Medicare & Medicaid Innovation under the Transforming Clinical Practice Initiative, the Agency for Healthcare Research and Quality (grants R01HS025164, R01HS025402, R03HS025517 and K12HS026379), the National Heart, Lung and Blood Institute of the National Institutes of Health (grants R56HL130496, R01HL131535 and R01HL151662), the National Science Foundation, the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology, and the Patient-Centered Outcomes Research Institute to develop a Clinical Data Research Network. FT is an employee of Pear Therapeutics, that develops and distributes prescription digital therapeutics for health concerns and disease. Other authors report no other conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2022 The Authors.)

Data on depression and stress among patients with spontaneous coronary artery dissection (SCAD) are limited. Using data from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study, which prospectively enrolled 3,572 acute myocardial infarction (AMI) patients between 18 and 55 years of age, we identified 67 SCAD cases. We compared Patient Health Questionnaire-9 (PHQ-9) and 14-item Perceived Stress Scale (PSS-14) scores obtained at baseline, 1 month, and 12 months between SCAD and AMI of all other causes. Using longitudinal linear mixed-effects analysis, we compared depression and stress scores between SCAD and other AMI, adjusting for time and selected covariates. Patients with SCAD had lower baseline PHQ-9 scores (6.1 ± 6.0 vs 7.7 ± 6.4 for other patients with AMI, p = 0.03), similar 1-month scores, and lower 12-month scores (3.2 ± 4.3 vs 4.9 ± 5.5, p = 0.004). At baseline and 1 month, patients with SCAD had similar PSS-14 scores to those of other patients with AMI. At 12 months, patients with SCAD had lower scores (18.4 ± 8.8 vs 21.5 ± 9.3 for other patients with AMI, p = 0.009). After adjustment for cardiovascular risk factors, co-morbidities, and clinical acuity, no differences in PHQ-9 or PSS-14 scores remained between SCAD and other AMI. Similar results were obtained in a subgroup analysis of only women with SCAD and other AMI. In conclusion, patients with SCAD had a relatively lower burden of depression and perceived stress than other patients with AMI, potentially because of fewer co-morbidities and favorable socioeconomic factors. However, given high depression and stress burden in both SCAD and other patients with AMI, routine screening can help identify and treat these patients., Competing Interests: Disclosures Dr. Bueno receives research funding from the Instituto de Salud Carlos III, Spain (PIE16/00021 and PI17/01799), Sociedad Española de Cardiología, Astra-Zeneca, Bayer, PhaseBio, and Novartis; has received consulting fees from Astra-Zeneca, Novartis, and Organon; speaking fees from Novartis, and is a scientific advisor for MEDSCAPE-the heart.org. In the past 3 years, Dr. Krumholz received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Reality Labs, Tesseract/4Catalyst, F-Prime, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, and Martin/Baughman Law Firm. He is a co-founder of Refactor Health and HugoHealth, and is associated with contracts, through Yale New Haven Hospital, with the Centers for Medicare & Medicaid Services and through Yale University with Johnson & Johnson. The remaining authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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 [β] -31.7; 95% CI: -51.2, -12.2) and higher cardiac index (β 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 (β 120.4; 95% CI: 102.4, 138.5) but lower cardiac index (β -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., Competing Interests: Yuan Lu is supported by the National Heart, Lung, and Blood Institute (K12HL138037) and the Yale Center for Implementation Science. She was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion. Erica S. Spatz receives support from the Food and Drug Administration to support projects within the Yale-Mayo Clinic Center of Excellence in Regulatory Science and Innovation (CERSI); the National Institute on Minority Health and Health Disparities (U54MD010711-01) to study precision-based approaches to diagnosing and preventing hypertension; and the National Institute of Biomedical Imaging and Bioengineering (R01EB028106-01) to study a cuff-less blood pressure device. Xin Zheng is supported by the CAMS Innovation Fund for Medical Science (2016-I2M-1-006), the National Key Research and Development Program (2016YFE0103800) from the Ministry of Science and Technology of China. Hui Lu is supported by the National Key R&D Program of China (2018YFC0910500) and Neil Shen’s SJTU Medical Research Fund. Zheng J. Ma is affiliated with Beijing Li-Heng Medical Technologies, Ltd, which designed the ICG device used in this study. Harlan Krumholz works under contract with the Centers for Medicare & Medicaid Services to support quality measurement programs; was a recipient of a research grant, through Yale, from Medtronic and the U.S. Food and Drug Administration to develop methods for post-market surveillance of medical devices; was a recipient of a research grant with Medtronic and is the recipient of a research grant from Johnson & Johnson, through Yale University, to support clinical trial data sharing; was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; receives payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation, from the Ben C. Martin Law Firm for work related to the Cook IVC filter litigation, and from the Siegfried and Jensen Law Firm for work related to Vioxx litigation; chairs a Cardiac Scientific Advisory Board for UnitedHealth; was a participant/participant representative of the IBM Watson Health Life Sciences Board; is a member of the Advisory Board for Element Science, the Advisory Board for Facebook, and the Physician Advisory Board for Aetna; and is the founder of HugoHealth, a personal health information platform, and co-founder of Refactor Health, an enterprise healthcare AI-augmented data management company. The other co-authors report no potential competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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.

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.

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.

Purpose: Physical inactivity, a modifiable risk factor for cardiovascular disease, is independently associated with stroke. Though some prior data have suggested sex differences in levels of physical activity, whether there are sex differences in the role of physical activity in primary stroke prevention is largely unknown. This systematic review identifies and describes recent findings on sex differences in the association between physical activity and incident (first-ever) stroke. This review also describes the current evidence on the strength of the association between physical activity and a reduced stroke risk in women in particular., Methods: Using a prespecified strategy, PubMed/MEDLINE and Cochrane Central were searched to identify observational studies or trials published from 2000 to 2020 and reporting sex differences in physical activity and incident stroke. To be included, among other criteria, studies had to include sex-specific effect estimates from women, men, or both. Titles, abstracts, and full-text articles were screened to identify studies meeting the inclusion criteria, and adjusted sex-specific estimates of the association between physical activity and incident stroke for total stroke (ischemic plus hemorrhagic) or ischemic stroke were abstracted., Findings: Thirty-seven studies met the inclusion criteria. Of 17 studies that included data on total incident stroke (ischemic and hemorrhagic combined) in both women and men, 7 (41%) showed similar associations between physical activity and incident stroke between women and men, 6 (35%) suggested a significant effect in women but not in men, and 3 (18%) showed a significant effect in men but not in women. Of 10 studies that included data on ischemic stroke in women and men, 5 (50%) suggested similar effects in women and men, 4 (40%) suggested a significant effect in women but not in men, and 1 (10%) showed an effect in men but not women. In women specifically, the majority of included studies demonstrated a reduced risk for incident stroke with physical activity, with relative risk reductions ranging from 11% to 72%, though most estimates fell between 20% and 40%., Implications: The majority of studies indicated a clear association between physical activity and a reduction in stroke risk. Studies were split as to the potential for sex differences in this association. Future prospective investigations should identify strategies for the use of increased physical activity for primary stroke prevention, with sex-specific considerations as warranted. The data on sex-specific dose-response relationship between physical activity and stroke risk are inconclusive and warrant more research., Competing Interests: DECLARATION OF INTEREST Supported by NHLBI grant K23 HL140081-01A1 (T.E.M.); Canadian Institutes of Health Research grants (A.P. and R.P.D.); a Heart and Stroke Foundation of Canada National New Investigator award (A.Y.X.Y.); National Heart Foundation Australia award 102742 (C.C.); Lone Star Stroke Research Consortium and American Heart Association grant 847469 (A.N.D.); NIH/National Center for Advancing Translational Sciences (NCATS) Colorado CTSA grant KL2 TR002534 (M.L.); NIH grants R01 MD012467 (T.R.), R01 NS029993 (T.R.), R01 NS040807 (T.R.), U24 NS107267 (T.R.), U24NS107235 (C.B.), and UL2TR001420 (C.B.); NCATS grants UL1 TR002736 and KL2 TR002737 (T.R.); a Florida Department of Health grant (T.R.); an American Heart Association grant (R.P.D.); Agency for Healthcare Research Quality grant 1R01HS025723 (C.B.); and Patient Centered Outcomes Research Institute Phased Large Awards for Comparative Effectiveness Research (C.B.). The authors have indicated that they have no conflicts of interest with regard to the content of this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Data on health status outcomes after spontaneous coronary artery dissection (SCAD) are limited., Methods and Findings: Using the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study we compared patients with SCAD and other acute myocardial infarction (AMI) at presentation (baseline), 1-month, and-12 months using standardized health status instruments. Among 3572 AMI patients ≤ 55 years, 67 had SCAD. SCAD patients were younger (median age (IQR) 45 (40.5-51) years vs. 48 (44-52) in other AMI, p = 0.003), more often female (92.5% vs. 66.6%), have college education (73.1% vs. 51.7%) and household income >$100,000 (43.3% vs. 17.7% (All p<0.001). SCAD patients at baseline had higher mean ± SD Short Form-12 [SF-12] physical component scores [PCS] (48.7±10.2 vs. 43.8±12.1, p<0.001) and mental component scores [MCS] (49.6±12.4 vs. 45.4±12.5, p = 0.008), and at 12-months [PCS (50.1±9.0 vs. 44.3±12.3, p<0.001) and MCS (53±10.1 vs 50.2±11.0, p = 0.045)]. The Euro-Quality of Life Scale [EQ-5D] VAS and EQ-5D index scores were similar at baseline, but higher at 12-months for SCAD (EQ-5D VAS: 82.2±10.2 vs. 72.3±21.0, p<0.001; EQ-5D index scores; 90.2±15.3 vs. 83.7±19.8, p = 0.012). SCAD patients had better baseline Seattle Angina Questionnaire [SAQ] physical limitation (88.8±20.1 vs. 81.2±25.4, p = 0.017). At 12-months SCAD patients had better physical limitation (98.0±8.5 vs. 91.4±18.8, p = 0.007), angina frequency (96.4±8.8 vs. 91.3±16.8, p = 0.018) and quality of life scores (80.7±14.7 vs 72.2±23.2, p = 0.005). Magnitude of change in health status from baseline to 12-months was not statistically different between the groups. After adjustment for time and comorbidities there remained no difference in most health status outcomes., Conclusions: SCAD patients fare marginally better than other AMI patients on most health status instruments and have similar 12-month health status recovery. Better pre-event health status suggests a need to modify exercise prescriptions and cardiac rehabilitation protocols to better assist this physically active population to recover., Competing Interests: The authors have declared that no competing interests exist.

Background: Clinicians make a medical diagnosis by recognizing diagnostic possibilities, often using memories of prior examples. These memories, called "exemplars," reflect specific symptom combinations in individual patients, yet most clinical studies report how symptoms aggregate in populations. We studied how symptoms of acute myocardial infarction combine in individuals as symptom phenotypes and how symptom phenotypes are distributed in women and men., Methods: In this analysis of the SILVER-AMI Study, we studied 3041 patients (1346 women and 1645 men) 75 years of age or older with acute myocardial infarction. Each patient had a standardized in-person interview during the acute myocardial infarction admission to document the presenting symptoms, which enabled a thorough examination of symptom combinations in individuals. Specific symptom combinations defined symptom phenotypes and distributions of symptom phenotypes were compared in women and men using Monte Carlo permutation testing and repeated subsampling., Results: There were 1469 unique symptom phenotypes in the entire SILVER-AMI cohort of patients with acute myocardial infarction. There were 831 unique symptom phenotypes in women, as compared with 819 in men, which was highly significant, given the larger number of men than women in the study (P < .0001). Women had significantly more symptom phenotypes than men in almost all acute myocardial infarction subgroups., Conclusions: Older patients with acute myocardial infarction have enormous variation in symptom phenotypes. Women reported more symptoms and had significantly more symptom phenotypes than men. Appreciation of the diversity of symptom phenotypes may help clinicians recognize the less common phenotypes that occur more often in women., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background Sex differences in health status outcomes after percutaneous coronary intervention among patients without acute myocardial infarction are not well described. Methods and Results A total of 2237 patients (33.4% women) without acute myocardial infarction undergoing percutaneous coronary intervention were enrolled from 39 Chinese tertiary hospitals in the PEACE (China Patient-centered Evaluative Assessment of Cardiac Events) prospective percutaneous coronary intervention study. Data were collected immediately before and 1 year following percutaneous coronary intervention. Health status was measured using the disease-specific Seattle Angina Questionnaire (SAQ) Angina Frequency and Quality of Life domains, as well as the SAQ Summary Score. Among the study population, women were older, more often single, had lower levels of education, and had a higher prevalence of cardiac risk factors such as hypertension and diabetes mellitus. Women had lower mean 1-year SAQ Angina Frequency scores (mean±SD, 91.0±17.3 versus 93.9±13.3; P <0.01), SAQ Quality of Life scores (mean±SD, 67.3±23.0 versus 70.6±21.6; P <0.01), and SAQ Summary Scores (mean±SD, 81.6±13.8 versus 84.8±11.9; P <0.01), a difference of marginal clinical significance that persisted after multivariable adjustment. A slightly larger improvement in the SAQ Summary Score was observed in women as compared with men (20.9±22.6 versus 18.5±21.3; P =0.007) in unadjusted analysis. However, women were less likely to achieve clinically significant improvement in SAQ Angina Frequency (adjusted odds ratio, 0.67; 95% CI, 0.45-1.00) and SAQ Quality of Life (adjusted odds ratio, 0.73; 95% CI, 0.56-0.96) after adjustment. Conclusions There were no clinically significant differences in 1-year health status outcomes and improvement in health status by sex among patients without acute myocardial infarction following percutaneous coronary intervention. However, female sex was associated with poorer 1-year health status and a lower likelihood of experiencing clinically improvement in health status. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01624922.

Background: The diagnosis of acute myocardial infarction (AMI) is missed more frequently in young women than men, which may be related to the cognitive psychology of the diagnostic process. Physicians start the diagnostic process by intuitively recognizing familiar symptom phenotypes, but little is known about how symptoms combine in individuals as unique symptom phenotypes. We examined how symptoms of AMI combine as unique symptom phenotypes in individual patients to compare the distribution of symptom phenotypes in women versus men., Methods and Results: The VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) was a multicenter, observational cohort study of 3501 young adults hospitalized with AMI. Data were collected on presenting symptoms with standardized interviews and from medical record abstraction. The number and distribution of unique symptom phenotypes were compared between women and men. Because of the 2:1 female-to-male enrollment ratio, women and men were compared with permutation testing and repeated subsampling. There were 426 interview-symptom phenotypes in women and 280 in men. The observed difference between women and men of 146 phenotypes was significant, even allowing for the greater enrollment of women (permutation P =0.004, median difference 110 under the null hypothesis of no association between sex and phenotype). The repeated subsample analysis also showed significantly more interview-symptom phenotypes in women than men (206.8±7.3 versus 188.6±6.0, P <0.001). Women were more broadly distributed among symptom phenotype subgroups than men ( P <0.001). Similar findings were observed in the analysis of symptoms abstracted from the medical record., Conclusions: Women exhibited substantially more variation in unique symptom phenotypes than men, regardless of whether the symptoms were derived from structured interviews or abstracted from the medical record. These findings may provide an explanation for the higher missed diagnosis rate in young women with AMI and may have important implications for teaching and improving clinicians' ability to recognize the diagnosis of AMI in women.

Background: Studies of sex-based differences in older adults with acute myocardial infarction (AMI) have yielded mixed results. We, therefore, sought to evaluate sex-based differences in presentation characteristics, treatments, functional impairments, and in-hospital complications in a large, well-characterized population of older adults (≥75 years) hospitalized with AMI., Methods and Results: We analyzed data from participants enrolled in SILVER-AMI (Comprehensive Evaluation of Risk Factors in Older Patients With Acute Myocardial Infarction)-a prospective observational study consisting of 3041 older patients (44% women) hospitalized for AMI. Participants were stratified by AMI subtype (ST-segment-elevation myocardial infarction [STEMI] and non-STEMI [NSTEMI]) and subsequently evaluated for sex-based differences in clinical presentation, functional impairments, management, and in-hospital complications. Among the study sample, women were slightly older than men (NSTEMI: 82.1 versus 81.3, P <0.001; STEMI: 82.2 versus 80.6, P <0.001) and had lower rates of prior coronary disease. Women in the NSTEMI subgroup presented less frequently with chest pain as their primary symptom. Age-associated functional impairments at baseline were more common in women in both AMI subgroups (cognitive impairment, NSTEMI: 20.6% versus 14.3%, P <0.001; STEMI: 20.6% versus 12.4%, P =0.001; activities of daily living disability, NSTEMI: 19.7% versus 11.4%, P <0.001; STEMI: 14.8% versus 6.4%, P <0.001; impaired functional mobility, NSTEMI: 44.5% versus 30.7%, P <0.001; STEMI: 39.4% versus 22.0%, P <0.001). Women with AMI had lower rates of obstructive coronary disease (NSTEMI: P <0.001; STEMI: P =0.02), driven by lower rates of 3-vessel or left main disease than men (STEMI: 38.8% versus 58.7%; STEMI: 24.3% versus 32.1%), and underwent revascularization less commonly (NSTEMI: 55.6% versus 63.6%, P <0.001; STEMI: 87.3% versus 93.3%, P =0.01). Rates of bleeding were higher among women with STEMI (26.2% versus 15.6%, P <0.001) but not NSTEMI (17.8% versus 15.7%, P =0.21). Women had a higher frequency of bleeding following percutaneous coronary intervention with both NSTEMI (11.0% versus 7.8%, P =0.04) and STEMI (22.6% versus 14.8%, P =0.02)., Conclusions: Among older adults hospitalized with AMI, women had a higher prevalence of age-related functional impairments and, among the STEMI subgroup, a higher incidence of overall bleeding events, which was driven by higher rates of nonmajor bleeding events and bleeding following percutaneous coronary intervention. These differences may have important implications for in-hospital and posthospitalization needs.

Background Readmission after acute myocardial infarction in low- and middle-income countries like China is not well characterized. Methods and Results We approached consecutive patients with acute myocardial infarction hospitalized within 24 hours of symptom onset and discharged alive from 53 geographically diverse hospitals in China. We described rates of unplanned 30-day readmission, their timing and admitting diagnoses, and fit Cox proportional hazards models to identify factors associated with readmission. Among 3387 patients, median (interquartile range) age was 61 (52-69) years, and 76.9% were men. The index median length of stay was 11 (8-14) days. Unplanned 30-day readmission occurred in 6.3% of the cohort; most readmissions (77.7%) were for cardiovascular diagnoses. Nearly half (41.9% of all-cause readmissions; 44.3% of cardiovascular readmissions) occurred within 5 days of discharge. Mini-Global Registry of Acute Coronary Events scores at admission (hazard ratio [HR], 1.15 for every 10-point increase; 95% CI, 1.05-1.25), longer length of stay (HR, 1.03; 95% CI, 1.00-1.06 for each extra day), and in-hospital recurrent angina (HR, 1.40; 95% CI, 1.04-1.89) were associated with higher unplanned all-cause readmission. Revascularization during the index hospitalization (70.2% of the cohort) was associated with lower risks of all-cause readmission (HR, 0.27; 95% CI, 0.18-0.42). In addition, left ventricular ejection fraction <0.4 (HR, 1.79; 95% CI, 1.05-3.07) and in-hospital complication (HR, 1.20; 95% CI, 1.03-1.39) were associated with higher risk of unplanned cardiovascular readmission, and ST-segment-elevation myocardial infarction (HR, 0.60; 95% CI, 0.36-0.98) was associated with lower risk of unplanned cardiovascular readmission. Sex, family income, depression, stress level, lower social support, disease-specific health status, and medications were not associated with readmission. Conclusions In China, most readmissions are for cardiovascular events, and almost half occur within 5 days of discharge. Clinical factors identify patients at higher and lower unplanned readmissions. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01624909.

Purpose of Review: To explain sex and gender approaches to studying acute myocardial infarction (AMI) risk and outcomes in younger women (18-55 years). More specifically, by looking at the AMI care pathway-from AMI risk to receiving acute and follow-up outpatient care to longer term AMI outcomes-we will examine where potential psychosocial factors may be associated with inequalities in AMI care and outcomes in younger women., Recent Findings: Despite recent declines in AMI incidence, morbidity, and mortality rates, younger women stand out as a group whose incidence has risen and who face worse outcomes following AMI, as compared with other groups. A focus on gender, rather than the binary, biological sex construct, allowed researchers to better understand potential pathways as to why younger women are facing this risk. Feminine traits and disproportionate exposures to psychosocial stressors in society at large may be correlated with inequalities in AMI care and further AMI outcomes in younger women. Psychosocial interventions in women with AMI that have proven to be successful have embraced this wider gender concept. Adopting a wider gender-concept to understand roles and demands that are placed on individuals that make them more at risk to experience psychosocial stressors and make it more challenging to organize self-care, get access to care, and equitable care may be needed.

Background: We examined sex differences in long-term health outcomes following acute myocardial infarction in China, including mortality, major adverse cardiac events and health status (symptoms, functioning, quality of life)., Methods: A total of 3415 acute myocardial infarction patients (23.2% women) aged ⩾18 years were enrolled across 10 geographic regions in China (2012-2014) in the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) study. Clinical data was abstracted from medical records. Generic (Euro-Quality of Life Scale) and disease-specific (Seattle Angina Questionnaire) health status was obtained through interviews at baseline and one year., Results: At one year, women with acute myocardial infarction had a higher risk of death from all causes ( p<0.001), but had similar rates of major adverse cardiac events ( p=0.2). Women had lower mean generic (Euro-Quality of Life Scale utility index score: 0.90±0.13 vs 0.94±0.11) and disease specific health scores indicating poorer functioning (Seattle Angina Questionnaire summary score: 75.3±11.4 vs 78.4±9.7) and higher rates of daily/weekly angina (Seattle Angina Questionnaire angina frequency score ⩽60 vs >60: 9.1% vs 4.7%; all p<0.001). In multivariable analysis, there was a significant association between female sex and mortality (β=0.45, standard error=0.21, p=0.03) but not for major adverse cardiac events (β=-0.02, standard error=0.14, p=0.89). The association between female sex and worse generic health status persisted (β=-0.02, standard error=0.01, p=0.003), but was no longer significant between sexes for disease-specific health status (β=-0.82, standard error=0.58, p=0.154) or daily/weekly angina (odds ratio=1.39; 95% confidence interval 0.88-2.21)., Conclusion: Women in China have higher crude rates of all-cause/cardiovascular death versus men, as well as worse generic/disease specific health status at one-year post-acute myocardial infarction. The association between female sex and worse generic health status persisted following adjustment.

Importance: Return to work is an important indicator of recovery after acute myocardial infarction. Little is known, however, about the rate of returning to work within the year after an acute myocardial infarction in China, as well as the factors associated with returning to work after an acute myocardial infarction., Objectives: To determine the rate of return to work within 12 months after acute myocardial infarction, classify the reasons why patients did not return to work, and identify patient factors associated with returning to work., Design, Setting, and Participants: This prospective cohort study, conducted in 53 hospitals across 21 provinces in China, identified 1566 patients who were employed at the time of the index acute myocardial infarction hospitalization and participating in the China Patient-centered Evaluative Assessment of Cardiac Events Prospective Study of Acute Myocardial Infarction. Data collected included patients' baseline characteristics; employment status at 12 months after acute myocardial infarction; and, for those who were not employed at 12 months, potential reasons for not returning to work. A logistic regression model was fitted to identify factors associated with returning to work at 12 months. Data were collected from January 1, 2013, through July 17, 2014, and statistical analysis was conducted from August 9, 2016, to August 15, 2018., Main Outcomes and Measures: Return to work, defined as rejoining the workforce within 12 months after discharge from hospitalization for the index acute myocardial infarction., Results: Of 1566 patients (130 women and 1436 men; mean [SD] age, 52.2 [9.7] years), 875 patients (55.9%; 95% CI, 53.4%-58.3%) returned to work by 12 months after acute myocardial infarction. Among the 691 patients who did not return to work, 287 (41.5%) were unable to work and/or preferred not to work because of acute myocardial infarction and 131 (19.0%) retired early owing to the acute myocardial infarction. Female sex (relative risk, 0.65; 95% CI, 0.41-0.88), a history of smoking (relative risk, 0.82; 95% CI, 0.65-0.98), and in-hospital complications during the index acute myocardial infarction (relative risk, 0.96; 95% CI, 0.93-0.99) were associated with a lower likelihood of returning to work., Conclusions and Relevance: Almost half of the previously employed Chinese patients did not return to work within 12 months after acute myocardial infarction. Female sex, history of smoking, and in-hospital complications were associated with a lower likelihood of returning to work., Trial Registration: ClinicalTrials.gov Identifier: NCT01624909.

Young women with acute myocardial infarction (AMI) have a worse prognosis than their male counterparts. We searched for differences in the electrocardiographic presentation of men and women in a large, contemporary registry of young adults with AMI that could help explain gender differences in outcomes. The qualifying electrocardiogram was blindly assessed by a central core lab in 3,354 patients (67% women) aged 18 to 55 years included in the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients study. Compared with men, women did not have a different frequency of sinus rhythm, and they had shorter PR and QRS intervals and longer QTc intervals. Intraventricular conduction disturbances were not different among genders. Notably, women were more likely than men to have abnormal Q waves in anterior leads and a lower frequency of Q waves in other territories. ST-segment elevation myocardial infarction (STEMI) diagnosis was less frequent in women than in men (44.6% vs 55.1%, p < 0.001). Among patients with STEMI, women had less magnitude and extent of ST-segment elevation than men. In patients with non-STEMI, the frequency, magnitude, and extent of ST-segment depression were not different among genders, but women had anterior ST-segment depression less frequently and anterior negative T waves more frequently compared with men. These differences remained statistically significant after adjusting for baseline characteristics. In conclusion, there are significant gender differences in the electrocardiographic presentation of AMI among young patients. Further studies are warranted to evaluate their impact on gender-related differences in the management and outcomes of AMI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background and Aims: While high-sensitivity C-reactive protein (hs-CRP) is a marker of inflammation and higher cardiovascular risk, its association with health status (symptoms, function and quality of life) after acute myocardial infarction (AMI) is unknown., Methods: Among 3410 patients with AMI from the TRIUMPH (N = 1301) and VIRGO (N = 2109) studies, we compared 1-year generic (Medical Outcome Study Short Form-12 and Euro Quality of Life Visual Analog Scale) and disease-specific (Seattle Angina Questionnaire) health status outcomes in those with hs-CRP ≥2 mg/L vs. <2 mg/L. In hierarchical linear regression models, we examined the association of 30-day hs-CRP levels with 1-year health status without adjustment, after adjusting for 30-day health status, and after adjusting for demographic, socioeconomic, disease severity/comorbidities and treatment characteristics., Results: The median (25th, 75th percentiles) 30-day hs-CRP was 2.6 (1.1, 6.1) mg/L and 59% had hs-CRP ≥2 mg/L. Statin therapy was used in 92% of patients at hospital discharge. Thirty-day hs-CRP ≥2 mg/L was inversely associated with all 1-year health status measures in unadjusted and partially adjusted models, but not in fully-adjusted models. Results were similar when hs-CRP was analyzed as a continuous variable., Conclusions: While elevated hs-CRP 30 days after AMI was associated with worse health status in unadjusted analyses, this was not significant after adjusting for comorbidities, suggesting that hs-CRP may be a marker of comorbidities associated with worse health status. Whether reducing inflammation in AMI patients will improve health status should be tested in ongoing trials., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aims: Young women with acute myocardial infarction (AMI) have a higher risk of adverse outcomes than men. However, it is unclear how young women with AMI are different from young men across a spectrum of characteristics. We sought to compare young women and men at the time of AMI on six domains of demographic and clinical factors in order to determine whether they have distinct profiles., Methods and Results: Using data from Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO), a prospective cohort study of women and men aged ⩽55 years hospitalized for AMI ( n = 3501) in the United States and Spain, we evaluated sex differences in demographics, healthcare access, cardiovascular risk and psychosocial factors, symptoms and pre-hospital delay, clinical presentation, and hospital management for AMI. The study sample included 2349 (67%) women and 1152 (33%) men with a mean age of 47 years. Young women with AMI had higher rates of cardiovascular risk factors and comorbidities than men, including diabetes, congestive heart failure, chronic obstructive pulmonary disease, renal failure, and morbid obesity. They also exhibited higher levels of depression and stress, poorer physical and mental health status, and lower quality of life at baseline. Women had more delays in presentation and presented with higher clinical risk scores on average than men; however, men presented with higher levels of cardiac biomarkers and more classic electrocardiogram findings. Women were less likely to undergo revascularization procedures during hospitalization, and women with ST segment elevation myocardial infarction were less likely to receive timely primary reperfusion., Conclusions: Young women with AMI represent a distinct, higher-risk population that is different from young men.

Background: Compared with men, women are at higher risk of rehospitalization in the first month after discharge for acute myocardial infarction (AMI). However, it is unknown whether this risk extends to the full year and varies by age. Explanatory factors potentially mediating the relationship between sex and rehospitalization remain unexplored and are needed to reduce readmissions. The aim of this study was to assess sex differences and factors associated with 1-year rehospitalization rates after AMI., Methods: We recruited 3536 patients (33% women) ≥18 years of age hospitalized with AMI from 24 US centers into the TRIUMPH study (Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status). Data were obtained by medical record abstraction and patient interviews, and a physician panel adjudicated hospitalizations within the first year after AMI. We compared sex differences in rehospitalization using a Cox proportional hazards model, following sequential adjustment for covariates and testing for an age-sex interaction., Results: One-year crude all-cause rehospitalization rates for women were significantly higher than men after AMI (hazard ratio, 1.29 for women; 95% confidence interval, 1.12-1.48). After adjustment for demographics and clinical factors, women had a persistent 26% higher risk of rehospitalization (hazard ratio, 1.26; 95% confidence interval, 1.08-1.47). However, after adjustment for health status and psychosocial factors (hazard ratio, 1.14; 95% confidence interval, 0.96-1.35), the association was attenuated. No significant age-sex interaction was found for 1-year rehospitalization, suggesting that the increased risk applied to both older and younger women., Conclusions: Regardless of age, women have a higher risk of rehospitalization compared with men over the first year after AMI. Although the increased risk persisted after adjustment for clinical factors, the poorer health and psychosocial state of women attenuated the difference., (© 2017 American Heart Association, Inc.)

Background: Young women (≤55 years of age) with acute myocardial infarction (AMI) have higher mortality risk than similarly aged men. Elevated inflammatory markers are associated with an increased risk of cardiovascular outcomes after AMI, but little is known about whether young women have higher inflammatory levels after AMI compared with young men., Methods and Results: We assessed sex differences in post-AMI inflammatory markers and whether such differences account for sex differences in 12-month health status, using data from 2219 adults with AMI, 18 to 55 years of age, in the United States. Inflammatory markers including high-sensitivity C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 were measured 1 month after AMI. Overall, women had higher levels of hsCRP and lipoprotein-associated phospholipase A2 after AMI compared with men, and this remained statistically significant after multivariable adjustment. Regression analyses showed that elevated 1-month hsCRP was associated with poor health status (symptom, function, and quality of life) at 12 months. However, the association between hsCRP and health status became nonsignificant after adjustment for sociodemographics, comorbidities, and treatment factors. Half of these patients had residual inflammatory risk (hsCRP >3 mg/L) compared with a third who had residual cholesterol risk (Low-density lipoprotein cholesterol >100 mg/dL)., Conclusions: Young women with AMI had higher inflammatory levels compared with young men. Elevated 1-month hsCRP was associated with poor health status at 12 months after AMI, but this was attenuated after adjustment for patient characteristics. Targeted anti-inflammatory treatments are worthy of consideration for secondary prevention in these patients if ongoing trials of anti-inflammatory therapy prove effective., (© 2017 American Heart Association, Inc.)

Objectives: To characterize the magnitude and duration of risk of rehospitalization according to age after hospitalization for heart failure (HF), acute myocardial infarction (AMI), or pneumonia., Design: Retrospective cohort study., Setting: U.S. hospitals (n = 4,767)., Participants: All Medicare fee-for-service beneficiaries aged 65 and older surviving hospitalization for HF, AMI, or pneumonia between October 2012 and December 2013., Measurements: Daily risk of first rehospitalization for 1 year after hospital discharge was calculated according to age category (65-74, 75-84, ≥85) after adjustment for sex, race, comorbidities, and median ZIP code income. Time required for adjusted rehospitalization risk to decline 50% from maximum value after discharge, time required for adjusted risk to approach a plateau period of minimal day-to-day change, and degree to which adjusted risk was higher in recently hospitalized individuals than in the general elderly population were identified., Results: There were 414,720 hospitalizations for HF, 177,752 for AMI, and 568,304 for pneumonia. The adjusted risk of rehospitalization declined with increasing age after HF hospitalization (P < .001), rose with increasing age after AMI hospitalization (P < .001), and was slightly lower with increasing age after pneumonia hospitalization (P = .002). Adjusted risks of rehospitalization were high beyond 30 days after hospitalization for all ages., Conclusion: Although older age has heterogeneous relationships with rehospitalization risk, risk of readmission remains high for an extended time after discharge regardless of age or admitting condition. Condition-specific data on risk can be used to guide discussions on advanced care planning and strategies for longitudinal follow-up after hospitalization., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

In recent years, there has been growing public awareness and increasing attention to young women with acute myocardial infarction (AMI), who represent an extreme phenotype. Young women presenting with AMI may develop coronary disease by different mechanisms and often have worse recoveries, with higher risk for morbidity and mortality compared with similarly aged men. The purpose of this cardiovascular perspective piece is to review recent studies of AMI in young women. More specifically, we emphasize differences in the epidemiology, diagnosis, and management of AMI in young women (when compared with men) across the continuum of care, including their pre-AMI, in-hospital, and post-AMI periods, and highlight gaps in knowledge and outcomes that can inform the next generation of research., (© 2017 American Heart Association, Inc.)

Objective: The aim of the study was to examine how psychological stress changes over time in young and middle-aged patients after experiencing an acute myocardial infarction (AMI) and whether these changes differ between men and women., Methods: We analyzed data obtained from 2358 women and 1151 men aged 18 to 55 years hospitalized for AMI. Psychological stress was measured using the 14-item Perceived Stress Scale (PSS-14) at initial hospitalization and at 1 month and 12 months after AMI. We used linear mixed-effects models to examine changes in PSS-14 scores over time and sex differences in these changes, while adjusting for patient characteristics and accounting for correlation among repeated observations within patients., Results: Overall, patients' perceived stress decreased over time, especially during the first month after AMI. Women had higher levels of perceived stress than men throughout the 12-month period (difference in PSS-14 score = 3.63, 95% confidence interval = 3.08 to 4.18, p < .001), but they did not differ in how stress changed over time. Adjustment for patient characteristics did not alter the overall pattern of sex difference in changes of perceived stress over time other than attenuating the magnitude of sex difference in PSS-14 score (difference between women and men = 1.74, 95% confidence interval = 1.32 to 2.16, p < .001). The magnitude of sex differences in perceived stress was similar in patients with versus without post-AMI angina, even though patients with angina experienced less improvement in PSS-14 score than those without angina., Conclusions: In young and middle-aged patients with AMI, women reported higher levels of perceived stress than men throughout the first 12 months of recovery. However, women and men had a similar pattern in how perceived stress changed over time.

Background: Young women with acute myocardial infarction (AMI) have higher mortality risk than similarly aged men. An adverse lipid profile is an important risk factor for cardiovascular outcomes after AMI, but little is known about whether young women with AMI have a higher-risk lipid pattern than men. We characterized sex differences in lipid profiles and treatment utilization among young adults with AMI., Methods: A total of 2,219 adults with AMI (1,494 women) aged 18-55 years were enrolled from 103 hospitals in the United States (2008-2012). Serum lipids and lipoprotein subclasses were measured 1 month after discharge., Results: More than 90% of adults were discharged on a statin, but less than half received a high-intensity dose and 12% stopped taking treatments by 1 month. For both men and women, the median of low-density lipoprotein (LDL) cholesterol was reduced to <100 mg/dL 1 month after discharge for AMI, but high-density lipoprotein (HDL) cholesterol remained <40 mg/dL. Multivariate regression analyses showed that young women had favorable lipoprotein profiles compared with men: women had higher HDL cholesterol and HDL large particle, but lower total cholesterol-to-HDL cholesterol ratio and LDL small particle., Conclusions: Young women with AMI had slightly favorable lipid and lipoprotein profiles compared with men, suggesting that difference in lipid and lipoprotein may not be a major contributor to sex differences in outcomes after AMI. In both men and women, statin remained inadequately used, and low HDL cholesterol level was a major lipid abnormality., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Interpreting the clinical significance of changes in patient-reported outcomes (PROs) is critically important. The most commonly used approach is to anchor mean changes on PRO scores against a global assessment of change. Whether the assessor of global change should be patients or their physicians is unknown. We compared patients' and physicians' assessments of change over time to examine which was more aligned with patients' changes in PRO measures., Methods: A total of 459 chronic heart failure patients aged >30 years were enrolled from 13 US centers. Data were obtained by medical record abstraction, physical assessments, and patient interviews at a baseline clinic visit and 6 weeks later. Health status was measured with the disease-specific Kansas City Cardiomyopathy Questionnaire (KCCQ), and both patients and physicians completed a validated 15-level global assessment of change, ranging from large deterioration to large improvement., Results: There was substantial variation between physicians/patients' global assessment of clinical change (weighted kappa = 0.36, 95 % CI 0.28, 0.43). Overall, physician assessments were more strongly correlated with change on the KCCQ summary score than were patients' assessments (physician R = 0.37, patient R = 0.29)., Conclusion: There was substantial variation between patients' and physicians' global assessment of 6-week change in heart failure status. Physician assessments of the importance of clinical changes were more strongly associated with changes in all domains of patient-reported health status, as assessed by the KCCQ, and may provide a more consistent method for defining the clinical importance of changes in patients' health status.

Objectives: The aim of this study was to assess trends in hospitalizations and outcomes for Takotsubo cardiomyopathy (TTC)., Background: There is a paucity of nationally representative data on trends in short- and long-term outcomes for patients with TTC., Methods: The authors examined hospitalization rates; in-hospital, 30-day, and 1-year mortality; and all-cause 30-day readmission for Medicare fee-for-service beneficiaries with principal and secondary diagnoses of TTC from 2007 to 2012., Results: Hospitalizations for principal or secondary diagnosis of TTC increased from 5.7 per 100,000 person-years in 2007 to 17.4 in 2012 (p for trend < 0.001). Patients were predominantly women and of white race. For principal TTC, in-hospital, 30-day, and 1-year mortality was 1.3% (95% confidence interval [CI]: 1.1% to 1.6%), 2.5% (95% CI: 2.2% to 2.8%), and 6.9% (95% CI: 6.4% to 7.5%), and the 30-day readmission rate was 11.6% (95% CI: 10.9% to 12.3%). For secondary TTC, in-hospital, 30-day, and 1-year mortality was 3% (95% CI: 2.7% to 3.3%), 4.7% (95% CI: 4.4% to 5.1%), and 11.4% (95% CI: 10.8% to 11.9%), and the 30-day readmission rate was 15.8% (95% CI: 15.1% to 16.4%). Over time, there was no change in mortality or readmission rate for both cohorts. Patients ≥85 years of age had higher in-hospital, 30-day, and 1-year mortality and 30-day readmission rates. Among patients with principal TTC, male and nonwhite patients had higher 1-year mortality than their counterparts, whereas in those with secondary TTC, mortality was worse at all 3 time points. Nonwhite patients had higher 30-day readmission rates for both cohorts., Conclusions: Hospitalization rates for TTC are increasing, but short- and long-term outcomes have not changed. At 1 year, 14 in 15 patients with principal TTC and 8 in 9 with secondary TTC are alive. Older, male, and nonwhite patients have worse outcomes., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: We assessed gender differences in pre-event health status (symptoms, functioning, quality of life) in young patients with acute myocardial infarction and whether or not this association persists following sequential adjustment for important covariates. We also evaluated the interaction between gender and prior coronary artery disease, given that aggressive symptom control is a cornerstone of care in those with known coronary disease., Methods and Results: A total of 3501 acute myocardial infarction patients (2349 women) aged 18-55 years were enrolled from 103 US/24 Spanish hospitals (2008-2012). Clinical/health status information was obtained by medical record abstraction and patient interviews. Pre-event health status was measured by generic (Short Form-12, EuroQoL) and disease-specific (Seattle Angina Questionnaire) measures. T-test/chi-square and multivariable linear/logistic regression analysis was utilized, sequentially adjusting for covariates. Women had more co-morbidities and significantly lower generic mean health scores than men (Short Form-12 physical health = 43 ± 12 vs. 46 ± 11 and mental health = 44 ± 13 vs. 48 ± 11); EuroQoL utility index = 0.7 ± 0.2 vs. 0.8 ± 0.2 and visual analog scale = 63 ± 22 vs. 67 ± 20, P < 0.0001 for all. Their disease-specific health status was also worse, with more angina (Seattle Angina Questionnaire angina frequency = 83 ± 22 vs. 87 ± 18), worse physical function (physical limitation = 78 ± 27 vs. 87 ± 21) and poorer quality of life (55 ± 25 vs. 60 ± 22, P<0.0001 for all). In multivariable analysis, the association between female gender and worse generic physical/mental health persisted, as well as worse disease-specific physical limitation and quality of life. The interaction between gender and prior coronary artery disease was not significant in any of the health status outcomes., Conclusion: Young women have worse pre-event health status as compared with men, regardless of their coronary artery disease history. While future studies of gender differences should adjust for baseline health status, an opportunity may exist to better address the pre-event health status of women at risk for acute myocardial infarction., (© The European Society of Cardiology 2015.)

Background: Few studies have examined gender differences in health status and cardiovascular outcomes in patients with peripheral artery disease (PAD). This study assessed (1) self-reported health status at PAD diagnosis and 12-months later, and explored (2) whether outcomes in women with PAD differ with regard to long-term major adverse events., Methods and Results: A total of 816 patients (285 women) with PAD were enrolled from 2 vascular clinics in the Netherlands. Baseline clinical data and subsequent adverse events were recorded and patients completed the Short Form-12 (SF-12, Physical Component Score [PCS] and Mental Component Score [MCS]) upon PAD diagnosis and 12-months later. Women had similar ages and clinical characteristics, but poorer socio-economic status and more depressive symptoms at initial diagnosis, as compared with men. Women also had poorer physical (PCS: 37±10 versus 40±10, P=0.004) and mental (, Mcs: 47±12 versus 49±11, P=0.005) health status at the time of presentation. At 12-months, women still reported a poorer overall PCS score (41±12 versus 46±11, P=0.006) and MCS score (42±14 versus 49±12, P=0.002). Female gender was an independent determinant of a poorer baseline and 12-month PCS and MCS scores. However, there were no significant differences by gender on either mortality (unadjusted hazard ratio [HR]=0.93, 95% CI 0.60;1.44, P=0.74) or major adverse events (unadjusted HR=0.90, 95% CI 0.63;1.29, P=0.57), after a median follow-up of 3.2 years., Conclusions: Women's physical and mental health status is compromised both at initial PAD diagnosis and at 12-month follow-up, despite experiencing a similar magnitude of change in their health scores throughout the first 12-months after diagnosis., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: A delayed Door-to-Balloon (DTB) time in women with ST-elevation myocardial infarction (STEMI) has been associated with an increased mortality. The objectives of this study were to (a) quantify the components of the delayed DTB time in women and (b) assess the independent effect of gender on DTB time in patients undergoing percutaneous coronary intervention (PCI) for STEMI., Methods: Clinical parameters were prospectively collected for 735 STEMI patients undergoing primary PCI from 2006 to 2010, with particular attention to the components of DTB time, including the onset of chest pain and the 'code' notification of the STEMI team by the Emergency Department., Results: Women were significantly older with more co-morbidity. Upon hospital arrival they also experienced delays in Door-to-Code (23 vs. 17 min, P=.012), Code-to-Balloon (63 vs. 57 min, P=.001) and thus DTB time (88 vs. 72 min, P=.001). After multivariate adjustment, independent determinants of DTB time included female gender (ratio of geometric means [RGM]=1.13; 95% CI 1.02-1.26; P=.022), hypertension (RGM=1.12, 95% CI 1.02-1.23, P=.014), maximum ST-elevation (RGM=0.97, 95% CI 0.94-0.98, P<.001), office hours (RGM=0.84, 95% CI 0.78-0.92, P<.001) and triage category (RGM=1.23, 95% CI 1.09-1.40, P=.001)., Conclusions: Women experience delays in identification of the STEMI diagnosis and also in the PCI process. Thus a multifaceted approach addressing both the diagnosis and management of STEMI in women is required., (Copyright © 2013 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Several biologic and clinical factors contribute to the increased 30-day mortality and re-infarction rate in women with ST-segment elevation myocardial infarction (STEMI). Sex differences in cardiac hemodynamic parameters such as pulmonary capillary wedge pressure (PCWP) have not been examined and might play an important role. The objectives of the present study were to examine whether female sex is an independent determinant of PCWP during acute STEMI and whether an elevated PCWP contributes to all-cause 30-day mortality and re-infarction in women. The clinical, angiographic, and hemodynamic features of 470 consecutive patients with STEMI (n = 135 women) undergoing emergency coronary angiography with right-side heart catheterization were evaluated with respect to sex. Women had an elevated PCWP (20 ± 8 vs 16 ± 7 mm Hg, p <0.001) and reduced mixed venous oxygen saturation (67 ± 11% vs 71 ± 9%, p = 0.004). On multivariate analysis, female sex (β = 4.04, 95% confidence interval [CI] 2.04 to 6.04, p <0.001), hypertension (β = 2.07, 95% CI 0.31 to 3.83, p = 0.021), and creatine kinase-estimated infarct size (β = 0.001, 95% CI 0.001 to 0.002, p ≤0.001) were independent predictors of an elevated PCWP. Female sex exerted a minor independent effect on 30-day mortality and re-infarction (odds ratio 2.36, 95% CI 1.25 to 4.46, p = 0.008). However, once PCWP was entered into the mediation model, sex was no longer significant, suggesting that the effect of sex on the post-STEMI outcomes is potentially mediated through PCWP (odds ratio 1.07, 95% CI 1.02 to 1.12, p = 0.011). In conclusion, during acute STEMI, women have greater left ventricular filling pressures compared with men, independent of age, hypertension, and infarct size. The biologic explanation for this difference requires additional investigation, although it does not appear to contribute to the increased 30-day mortality and re-infarction rate observed in women., (Copyright © 2013 Elsevier Inc. All rights reserved.)