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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., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Dr. Spertus discloses providing consultative services on patient-reported outcomes and evidence evaluation to Alnylam, AstraZeneca, Bayer, Merck, Janssen, Bristol Meyers Squibb, Edwards, Kineksia, 4DT Medical, Terumo, Cytokinetics, Imbria, and United Healthcare. He holds research grants from Bristol Meyers Squibb, Abbott Vascular and Janssen. He owns the copyright to the Seattle Angina Questionnaire, Kansas City Cardiomyopathy Questionnaire, and Peripheral Artery Questionnaire and serves on the Board of Directors for Blue Cross Blue Shield of Kansas City. No other authors report having any other disclosures to report. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 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.)

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.

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.

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.

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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 β , 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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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.

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.)

Introduction: Peripheral artery disease (PAD) is a burdensome disease. It is unclear whether PAD cohorts enrolled in contemporary randomized control trials (RCT) are representative of the real-world PAD populations in terms of their patient characteristics., Methods: We compared baseline patient characteristics and health status (as measured by the Peripheral Artery Questionnaire [PAQ]) between the randomized CLEVER study, and the real-world PORTRAIT registry. CLEVER was an RCT of PAD patients enrolled from 29 centers across the US and Canada comparing revascularization with stenting versus optimal medical therapy (OMT) and supervised exercise therapy (SET) plus OMT. PORTRAIT was a multicenter, prospective study of patients with new or worsening PAD symptoms across ten sites in the US., Results: The final cohort consisted of 879 patients (n = 119 from CLEVER, n = 760 from PORTRAIT (24.5% black, 41.4% women). While CLEVER enrolled patients with aortoiliac disease, only 16.0% of the PORTRAIT cohort had isolated aortoiliac disease. Compared with CLEVER, patients from PORTRAIT were older (64.0 ± 9.5 versus 68.9 ± 9.5 yrs., p ≤0.001), had more severe disease as measured by the ankle brachial index (0.7 ± 0.2 versus 0.9 ± 0.2, p ≤0.001) and a higher prevalence of cardiovascular risk factors including hyperlipidemia and diabetes (all p values<0.05). Both cohorts had similar disease-specific health status as measured by the PAQ summary score (47.4 ± 21.9 versus 43.6 ± 18.4, p = 0.07)., Conclusion: In this comparative study, real-world patients with PAD were older and sicker when compared to an RCT with similar indications. This gap may be bridged by improving enrollment of underrepresented high-risk patients in PAD trials testing strategies for PAD symptom relief., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01419080?term=portrait&rank=1NCT01419080., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background Although there has been movement in cardiology to advance patient-centered approaches to postacute myocardial infarction (AMI) care, work remains to be done in aligning patient preferences with clinical care. Our objective was to characterize patients' experience of AMI and treatment to develop a new conceptual framework of patient-centered recovery in cardiology. Methods and Results We conducted in-depth interviews with people who previously experienced an AMI (2016-2019). The interview focused on participants' experiences of their recovery, which were audio-recorded, transcribed verbatim, and analyzed using a phenomenological framework. The overarching theme described by the 42 participants was feeling like a "different person" after the AMI. This shift manifested itself in both losses and gains, each of which posed new challenges to everyday life. The experience appeared to be an active process requiring people to take responsibility for their health. In terms of loss, participants describe how the AMI threatened their sense of safety and security and led to social isolation, fragility, uncertainty about the future, and difficulty expressing emotions accompanied this new fear. A conceptual framework describing the relationship between AMI, identity change, and functioning was developed. Conclusions Participants experienced the AMI as an unexpected disruption in their lives that had far-reaching effects on their daily functioning, and were resolved in numerous ways. The conceptual framework may assist in providing a theoretical basis for future interventions in cardiology that not only engage and retain patients in care but also improve long-term adherence to secondary prevention and other aspects of self-care.

Importance: Quality of care of young adults with acute myocardial infarction (AMI) may depend on health care systems in addition to individual-level factors such as biological sex and social determinants of health (SDOH)., Objective: To examine whether the quality of in-hospital and postacute care among young adults with AMI differs between the US and Canada and whether female sex and adverse SDOH are associated with a low quality of care., Design, Setting, and Participants: This retrospective cohort analysis used data from 2 large cohorts of young adults (aged ≤55 years) receiving in-hospital and outpatient care for AMI at 127 centers in the US and Canada. Data were collected from August 21, 2008, to April 30, 2013, and analyzed from July 12, 2019, to March 10, 2021., Exposures: Sex, SDOH, and health care system., Main Outcomes and Measures: Opportunity-based quality-of-care score (QCS), determined by dividing the total number of quality indicators of care received by the total number for which the patient was eligible, with low quality of care defined as the lowest tertile of the QCS., Results: A total of 4048 adults with AMI (2345 women [57.9%]; median age, 49 [interquartile range, 44-52] years; 3004 [74.2%] in the US) were included in the analysis. Of 3416 patients with in-hospital QCS available, 1061 (31.1%) received a low QCS, including more women compared with men (725 of 2007 [36.1%] vs 336 of 1409 [23.8%]; P < .001) and more patients treated in the US vs Canada (962 of 2646 [36.4%] vs 99 of 770 [12.9%]; P < .001). Conversely, low quality of post-AMI care (748 of 2938 [25.5%]) was similarly observed for both sexes, with a higher prevalence in the US (678 of 2346 [28.9%] vs 70 of 592 [11.8%]). In adjusted analyses, female sex was not associated with low QCS for in-hospital (odds ratio [OR], 1.05; 95% CI, 0.87-1.28) and post-AMI (OR, 1.07; 95% CI, 0.88-1.30) care. Conversely, being treated in the US was associated with low in-hospital (OR, 2.93; 95% CI, 2.16-3.99) and post-AMI (OR, 2.67; 95% CI, 1.97-3.63) QCS, regardless of sex. Of all SDOH, only employment was associated with higher quality of in-hospital care (OR, 0.72; 95% CI, 0.59-0.88). Finally, only in the US, low quality of in-hospital care was associated with a higher 1-year cardiac readmissions rate (234 of 962 [24.3%])., Conclusions and Relevance: These findings suggest that beyond sex, health care systems and SDOH that depict social vulnerability are associated with quality of AMI care. Taking into account SDOH among young adults with AMI may improve quality of care and reduce readmissions, especially in the US.

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

Background The extent to which race influences in-hospital quality of care for young adults (≤55 years) with acute myocardial infarction (AMI) is largely unknown. We examined racial disparities in in-hospital quality of AMI care and their impact on 1-year cardiac readmission. Methods and Results We used data from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study enrolling young Black and White US adults with AMI (2008-2012). An in-hospital quality of care score (QCS) was computed (standard AMI quality indicators divided by the total a patient is eligible for). Multivariable logistic regression was performed to identify factors associated with the lowest QCS tertile, including interactions between race and social determinants of health. Among 2846 young adults with AMI (median 48 years [interquartile range 44-52], 67.4% women, 18.8% Black race), Black individuals, especially women, exhibited a higher prevalence of cardiac risk factors and social determinants of health and were more likely to experience a non-ST-segment-elevation myocardial infarction than White individuals. Black individuals were more likely in the lowest QCS tertile than White individuals (40.8% versus 34.7%; P =0.003). The association between Black race and low QCS (odds ratio [OR], 1.25; 95% CI, 1.02-1.54) was attenuated by adjustment for confounders. Employment was independently associated with better QCS, especially among Black participants (OR, 0.76; 95% CI, 0.62-0.92; P- interaction =0.02). Black individuals experienced a higher rate of 1-year cardiac readmission (29.9% versus 20.0%; P <0.0001). Conclusions Black individuals with AMI received lower in-hospital quality of care and exhibited a higher rate of cardiac readmissions than White individuals. Black individuals had a lower quality of care if unemployed, highlighting the intersection of race and social determinants of health.

Background: Recovery from acute myocardial infarction (AMI) has been primarily understood in a narrow medical sense. For patients who survive, secondary prevention focuses largely on enhancing clinical outcomes. As a result, there is a lack of descriptive accounts of patients' experiences after AMI and little is known about how people go about the challenge of recovering from such an event., Objective: We conducted a meta-synthesis of the available literature on qualitative accounts of patients' experiences after AMI., Methods: We searched for relevant papers that were descriptive, qualitative accounts of participants' experiences after AMI across 4 electronic databases (April 2016). Using an adapted meta-ethnography approach, we analyzed the findings by translating studies into one another and synthesizing the findings from the studies., Results: After a review of titles/abstracts, reading each article twice in full, and cross-referencing articles, this process resulted in 17 studies with 224 participants (48% women) aged 23 to 90 years. All participants provided a first-person account of an AMI within the 3-day to 25-year time frame. Two major themes emerged that characterized patients' experiences: navigating lifestyle changes and navigating the emotional reaction to the event-consisting of various subthemes., Conclusion: Although AMI tends to be seen as a discrete event, participants are left with little professional guidance as to how to negotiate significant, and often discordant, psychosocial changes that have long-lasting effects on their lives, similar to persons with chronic illnesses but without research in place to figure out how to best support them., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine prevalence and characteristics of newly diagnosed diabetes (NDD) in younger adults hospitalised with acute myocardial infarction (AMI) and investigate whether NDD is associated with health status and clinical outcomes over 12-month post-AMI., Methods: In individuals (18-55 years) admitted with AMI, without established diabetes, we defined NDD as (1) baseline or 1-month HbA1c≥6.5%; (2) discharge diabetes diagnosis or (3) diabetes medication initiation within 1 month. We compared baseline characteristics of NDD, established diabetes and no diabetes, and their associations with baseline, 1-month and 12-month health status (angina-specific and non-disease specific), mortality and in-hospital complications., Results: Among 3501 patients in Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients study, 14.5% met NDD criteria. Among 508 patients with NDD, 35 (6.9%) received discharge diagnosis, 91 (17.9%) received discharge diabetes education and 14 (2.8%) initiated pharmacological treatment within 1 month. NDD was more common in non-White (OR 1.58, 95% CI 1.23 to 2.03), obese (OR 1.72, 95% CI 1.39 to 2.12), financially stressed patients (OR 1.27, 95% CI 1.02 to 1.58). Compared with established diabetes, NDD was independently associated with better disease-specific health status and quality of life (p≤0.04). No significant differences were found in unadjusted in-hospital mortality and complications between NDD and established or no diabetes., Conclusions: NDD was common among adults≤55 years admitted with AMI and was more frequent in non-White, obese, financially stressed individuals. Under 20% of patients with NDD received discharge diagnosis or initiated discharge diabetes education or pharmacological treatment within 1 month post-AMI. NDD was not associated with increased risk of worse short-term health status compared with risk noted for established diabetes., Trial Registration Number: NCT00597922., Competing Interests: Competing interests: HK, ES and KJL work under contract with the Centers for Medicare & Medicaid Services to develop publicly reported quality measures. In the past three years, HK received expenses and/or personal fees from UnitedHealth, IBM Watson Health, Element Science, Aetna, Facebook, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm, F-Prime, and the National Center for Cardiovascular Diseases in Beijing. He is an owner of Refactor Health and Hugo Health, and had grants and/or contracts from the Centers for Medicare & Medicaid Services, Medtronic, the U.S. Food and Drug Administration, Johnson & Johnson, and the Shenzhen Center for Health Information. HB receives research funding from the Instituto de Salud Carlos III, Spain (PIE16/00021 & PI17/01799), Astra-Zeneca, BMS, Janssen and Novartis; has received consulting fees from Astra-Zeneca, Bayer, BMS-Pfizer, Novartis and speaking fees or support for attending scientific meetings from Astra-Zeneca, Bayer, BMS-Pfizer, Novartis and MEDSCAPE-the heart.org. JAS is supported by grants from Bayer, serves as a consultant for Janssen, Bayer, Novartis, AstraZeneca and holds the copyright for the Seattle Angina Questionnaire with royalties paid. KJL is also supported by the National Institute on Aging and the American Federation of Aging Research through the Paul Beeson Career Development Award (K23AG04835)., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Despite investments to improve quality of emergency care for patients with acute myocardial infarction (AMI), few studies have described national, real-world trends in AMI care in the emergency department (ED). We aimed to describe trends in the epidemiology and quality of AMI care in US EDs over a recent 11-year period, from 2005 to 2015. Methods and Results We conducted an observational study of ED visits for AMI using the National Hospital Ambulatory Medical Care Survey, a nationally representative probability sample of US EDs. AMI visits were classified as ST-segment-elevation myocardial infarction (STEMI) and non-STEMI. Outcomes included annual incidence of AMI, median ED length of stay, ED disposition type, and ED administration of evidence-based medications. Annual ED visits for AMI decreased from 1 493 145 in 2005 to 581 924 in 2015. Estimated yearly incidence of ED visits for STEMI decreased from 1 402 768 to 315 813. The proportion of STEMI sent for immediate, same-hospital catheterization increased from 12% to 37%. Among patients with STEMI sent directly for catheterization, median ED length of stay decreased from 62 to 37 minutes. ED administration of antithrombotic and nonaspirin antiplatelet agents rose for STEMI (23%-31% and 10%-27%, respectively). Conclusions National, real-world trends in the epidemiology of AMI in the ED parallel those of clinical registries, with decreases in AMI incidence and STEMI proportion. ED care processes for STEMI mirror evolving guidelines that favor high-intensity antiplatelet therapy, early invasive strategies, and regionalization of care.

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.

Aims: The prognosis of patients with MINOCA (myocardial infarction with non-obstructive coronary arteries) is poorly understood. We examined major adverse cardiac events (MACE) defined as all-cause mortality, re-hospitalization for acute myocardial infarction (AMI), heart failure (HF), or stroke 12-months post-AMI in patients with MINOCA versus AMI patients with obstructive coronary artery disease (MICAD)., Methods and Results: Multicentre, observational cohort study of patients with AMI (≥65 years) from the National Cardiovascular Data Registry CathPCI Registry (July 2009-December 2013) who underwent coronary angiography with linkage to the Centers for Medicare and Medicaid (CMS) claims data. Patients were classified as MICAD or MINOCA by the presence or absence of an epicardial vessel with ≥50% stenosis. The primary endpoint was MACE at 12 months, and secondary endpoints included the components of MACE over 12 months. Among 286 780 AMI admissions (276 522 unique patients), 16 849 (5.9%) had MINOCA. The 12-month rates of MACE (18.7% vs. 27.6%), mortality (12.3% vs. 16.7%), and re-hospitalization for AMI (1.3% vs. 6.1%) and HF (5.9% vs. 9.3%) were significantly lower for MINOCA vs. MICAD patients (P < 0.001), but was similar between MINOCA and MICAD patients for re-hospitalization for stroke (1.6% vs. 1.4%, P = 0.128). Following risk-adjustment, MINOCA patients had a 43% lower risk of MACE over 12 months (hazard ratio = 0.57, 95% confidence interval 0.55-0.59), in comparison to MICAD patients. This pattern was similar for adjusted risks of the MACE components., Conclusion: This study confirms an unfavourable prognosis in elderly patients with MINOCA undergoing coronary angiography, with one in five patients with MINOCA suffering a major adverse event over 12 months., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

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 Diabetes mellitus increases the risk of mortality after acute myocardial infarction (AMI). However, little is known about the association of diabetes mellitus with post-AMI health status outcomes (symptoms, functioning, and quality of life) in younger adults. Methods and Results We investigated the association between diabetes mellitus and health status during the first 12 months after AMI, using data from 3501 adults with AMI (42.6% with diabetes mellitus) aged 18 to 55 years enrolled in the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study. Health status was measured with Seattle Angina Questionnaire (SAQ), 12-item Short-Form Health Survey, and EuroQol-Visual Analogue Scale at baseline hospitalization, 1-month, and 12-months post-AMI. At baseline, patients with diabetes mellitus had significantly worse SAQ-angina frequency (81±22 versus 86±19), SAQ-physical limitations (77±28 versus 85±23), SAQ-quality of life (55±25 versus 57±23), 12-item Short-Form Health Survey mental (44±13 versus 46±12)/physical functioning (41±12 versus 46±12), and EuroQol-Visual Analogue Scale (61±22 versus 66±21) than those without diabetes mellitus. Over time, both groups (with and without diabetes mellitus) improved considerably and the differences in health status scores progressively narrowed (except for 12-item Short-Form Health Survey physical functioning). In the linear-mixed effects models, adjusted for sociodemographics, cardiovascular risk factors, comorbidities, clinical characteristics, psychosocial factors, healthcare use, and AMI treatment, diabetes mellitus was associated with worse health status at baseline but not after discharge, and the association did not vary by sex. Conclusions At baseline, young adults with diabetes mellitus had poorer health status than those without diabetes mellitus. After AMI, however, they experienced significant improvements and diabetes mellitus was not associated with worse angina, SAQ-physical limitations, mental functioning, and quality of life, after adjustment for baseline covariates. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00597922.

Background: A sex-specific taxonomy was developed from the Variation in Recovery: Role of Gender Outcomes of Young AMI patients (VIRGO) study to better classify young women with AMI who received cardiac catheterization. We aim to determine whether this taxonomy is advantageous to the Universal Definition., Methods: We conducted a single-center retrospective chart review of consecutive women aged ≤55 years presenting with AMI between 1/1/2013 to 9/1/2016 who underwent cardiac catheterization during the index admission. The proportion of women classified using the Universal Definition of MI and VIRGO classification systems were compared., Results: Among women with AMI who underwent cardiac catheterization (n = 177), using the Universal Definition of MI, 68.4% were classified as Type 1, 11.9% as Type 2, and 2.3% as Type 4b; 17.5% were unclassified. Using the VIRGO taxonomy, most (68.4%) were classified as Class I (thrombosis/critical stenosis). The remaining patients were stratified by the presence of obstructive coronary artery disease (CAD) with demand (Class IIa: 4.0%) and without demand (Class IIb: 2.3%) versus non-obstructive CAD with demand (Class IIIa: 6.8%) and without demand (Class IIIb: 10.2%). Alternative discreet mechanisms (Class IV) were seen in 7.3%. Only 1.1% was unclassified., Conclusions: In a cohort of young women with AMI, 1 in 3 patients who underwent cardiac catheterization did not exhibit the classic mechanism of plaque disruption/thrombosis. By comparison, the VIRGO taxonomy classified more young women and further distinguished presentations within categories of the Universal Definition of MI. Application of this nuanced taxonomy may support the development of individualized diagnostic and treatment strategies in young women with AMI., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

Background: With over a decade of directed efforts to reduce sex and racial differences in coronary artery bypass grafting (CABG) utilization, and post-CABG outcomes, we sought to evaluate how the use of CABG and its outcomes have evolved in different sex and racial subgroups., Methods and Results: Using data on all fee-for-service Medicare beneficiaries undergoing CABG in the United States from 1999 to 2014, we examined differences by sex and race in calendar-year trends for CABG utilization and post-CABG outcomes (in-hospital, 30-day, and 1-year mortality and 30-day readmission). A total of 1 863 719 Medicare fee-for-service beneficiaries (33.6% women, 4.6% black) underwent CABG from 1999 to 2014, with a decrease from 611 to 245 CABG procedures per 100 000 person-years. Men compared with women and whites compared with blacks had higher CABG utilization, with declines in all subgroups. Higher post-CABG annual declines in mortality (95% confidence interval) were observed in women (in-hospital, -2.70% [-2.97, -2.44]; 30-day, -2.29% [-2.54, -2.04]; and 1-year mortality, -1.67% [-1.88, -1.46]) and blacks (in-hospital, -3.31% [-4.02, -2.60]; 30-day, -2.80% [-3.49, -2.12]; and 1-year mortality, -2.38% [-2.92, -1.84]), compared with men and whites, respectively. Mortality rates remained higher in women and blacks, but differences narrowed over time. Annual adjusted 30-day readmission rates remained unchanged for all patient groups., Conclusions: Women and black patients had persistently higher CABG mortality than men and white patients, respectively, despite greater declines over the time period. These findings indicate progress, but also the need for further progress., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: We compared the clinical characteristics and outcomes of young patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) versus obstructive disease (myocardial infarction due to coronary artery disease [MI-CAD]) and among patients with MINOCA by sex and subtype., Methods and Results: Between 2008 and 2012, VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) prospectively enrolled acute myocardial infarction patients aged 18 to 55 years in 103 hospitals at a 2:1 ratio of women to men. Using an angiographically driven taxonomy, we defined patients as having MI-CAD if there was revascularization or plaque ≥50% and as having MINOCA if there was <50% obstruction or a nonplaque mechanism. Patients who did not have an angiogram or who received thrombolytics before an angiogram were excluded. Outcomes included 1- and 12-month mortality and functional (Seattle Angina Questionnaire [SAQ]) and psychosocial status. Of 2690 patients undergoing angiography, 2374 (88.4%) had MI-CAD, 299 (11.1%) had MINOCA, and 17 (0.6%) remained unclassified. Women had 5 times higher odds of having MINOCA than men (14.9% versus 3.5%; odds ratio: 4.84; 95% confidence interval, 3.29-7.13). MINOCA patients were more likely to be without traditional cardiac risk factors (8.7% versus 1.3%; P <0.001) but more predisposed to hypercoaguable states than MI-CAD patients (3.0% versus 1.3%; P =0.036). Women with MI-CAD were more likely than those with MINOCA to be menopausal (55.2% versus 41.2%; P <0.001) or to have a history of gestational diabetes mellitus (16.8% versus 11.0%; P =0.028). The MINOCA mechanisms varied: a nonplaque mechanism was identified for 75 patients (25.1%), and their clinical profiles and management also varied. One- and 12-month mortality with MINOCA and MI-CAD was similar (1-month: 1.1% and 1.7% [ P =0.43]; 12-month: 0.6% and 2.3% [ P =0.68], respectively), as was adjusted 12-month SAQ quality of life (76.5 versus 73.5, respectively; P =0.06)., Conclusions: Young patients with MINOCA were more likely women, had a heterogeneous mechanistic profile, and had clinical outcomes that were comparable to those of MI-CAD patients., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00597922., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Young women (aged ≤55 years) with acute myocardial infarction (AMI) have poorer health status outcomes than similarly aged men. Low omega-3 fatty acids (FAs) have been implicated as risk factors for cardiovascular outcomes in AMI patients, but it is not clear whether young women have similar or different post-AMI omega-3 FA profiles compared with young men., Methods and Results: We assessed the sex differences in post-AMI omega-3 FAs and the associations of these biomarkers with patient-reported outcomes (symptom, functioning status, and quality of life) at 12-month follow-up, using data from 2985 US adults with AMI aged 18 to 55 years enrolled in the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young Acute Myocardial Infarction Patients) study. Biomarkers including eicosapentaenoic acid, docosahexaenoic acid, arachidonic acid (AA), eicosapentaenoic acid/AA ratio, omega-3/omega-6 ratio, and omega-3 index were measured 1 month after AMI. Overall, the omega-3 FAs and AA were similar in young men and women with AMI. In both unadjusted and adjusted analysis (controlling for age, sex, race, smoking, hypertension, diabetes mellitus, body mass index, and health status score at 1 month), omega-3 FAs and AA were not significantly associated with 12-month health status scores using the Bonferroni corrected statistical threshold., Conclusions: We found no evidence of sex differences in omega-3 FAs and AA in young men and women 1 month after AMI. Omega-3 FAs and AA at 1-month after AMI were generally not associated with 12-month patient-reported health status after adjusting for patient demographic, clinical characteristics, and the corresponding 1-month health status score., (© 2018 The Authors and Quest Diagnostics Inc. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Young women with ST-segment-elevation myocardial infarction experience reperfusion delays more frequently than men. Our aim was to determine the electrocardiographic correlates of delay in reperfusion in young patients with ST-segment-elevation myocardial infarction., Methods and Results: We examined sex differences in initial electrocardiographic characteristics among 1359 patients with ST-segment-elevation myocardial infarction in a prospective, observational, cohort study (2008-2012) of 3501 patients with acute myocardial infarction, 18 to 55 years of age, as part of the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study at 103 US and 24 Spanish hospitals enrolling in a 2:1 ratio for women/men. We created a multivariable logistic regression model to assess the relationship between reperfusion delay (door-to-balloon time >90 or >120 minutes for transfer or door-to-needle time >30 minutes) and electrocardiographic characteristics, adjusting for sex, sociodemographic characteristics, and clinical characteristics at presentation. In our study (834 women and 525 men), women were more likely to exceed reperfusion time guidelines than men (42.4% versus 31.5%; P <0.01). In multivariable analyses, female sex persisted as an important factor in exceeding reperfusion guidelines after adjusting for electrocardiographic characteristics (odds ratio, 1.57; 95% CI, 1.15-2.15). Positive voltage criteria for left ventricular hypertrophy and absence of a prehospital ECG were positive predictors of reperfusion delay; and ST elevation in lateral leads was an inverse predictor of reperfusion delay., Conclusions: Sex disparities in timeliness to reperfusion in young patients with ST-segment-elevation myocardial infarction persisted, despite adjusting for initial electrocardiographic characteristics. Left ventricular hypertrophy by voltage criteria and absence of prehospital ECG are strongly positively correlated and ST elevation in lateral leads is negatively correlated with reperfusion delay., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Elevated high-sensitivity C-reactive protein (hs-CRP) is associated with worse cardiovascular outcomes in patients with acute myocardial infarction (AMI), but little is known about the distribution of hs-CRP levels and predictors of elevated hs-CRP after AMI in the real world. Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status (TRIUMPH) and Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) are prospective AMI registries in the United States that assessed hs-CRP levels 30 days after AMI. TRIUMPH additionally assessed hs-CRP levels at the time of AMI and at 6 months. Hierarchical models were built to examine predictors of elevated hs-CRP (≥2.0 mg/L) at 30 days in both registries and at 6 months after AMI in TRIUMPH. Of 3410 patients in both registries, 58.6% had elevated hs-CRP 30 days after AMI. Patients with elevated hs-CRP at 30 days were more likely to be older, female, obese, smokers, report financial difficulties, and have higher low-density lipoprotein cholesterol levels on admission, diabetes, and hypertension. In TRIUMPH, baseline hs-CRP ≥2 mg/L (n = 1301) was significantly associated with elevated hs-CRP at follow-up (P < 0.001). Similar associations were found in TRIUMPH patients with elevated hs-CRP at 6 months. Our study identified a high prevalence and several patient characteristics associated with elevated hs-CRP at 1 and 6 months after discharge. Further studies to test routine screening after AMI may be warranted to identify higher-risk patients for more aggressive secondary prevention., (© 2017 Wiley Periodicals, Inc.)

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.)