Seasonal Variability and Shared Molecular Signatures of Inactivated Influenza Vaccination in Young and Older Adults.

The seasonal influenza vaccine is an important public health tool but is only effective in a subset of individuals. The identification of molecular signatures provides a mechanism to understand the drivers of vaccine-induced immunity. Most previously reported molecular signatures of human influenza vaccination were derived from a single age group or season, ignoring the effects of immunosenescence or vaccine composition. Thus, it remains unclear how immune signatures of vaccine response change with age across multiple seasons. In this study we profile the transcriptional landscape of young and older adults over five consecutive vaccination seasons to identify shared signatures of vaccine response as well as marked seasonal differences. Along with substantial variability in vaccine-induced signatures across seasons, we uncovered a common transcriptional signature 28 days postvaccination in both young and older adults. However, gene expression patterns associated with vaccine-induced Ab responses were distinct in young and older adults; for example, increased expression of killer cell lectin-like receptor B1 (KLRB1; CD161) 28 days postvaccination positively and negatively predicted vaccine-induced Ab responses in young and older adults, respectively. These findings contribute new insights for developing more effective influenza vaccines, particularly in older adults.

Predicting 6-Month Mortality for Older Adults Hospitalized With Acute Myocardial Infarction: A Cohort Study.

Background: Older adults with acute myocardial infarction (AMI) have higher prevalence of functional impairments, including deficits in cognition, strength, and sensory domains, than their younger counterparts. Objective: To develop and evaluate the prognostic utility of a risk model for 6-month post-AMI mortality in older adults that incorporates information about functional impairments. Design: Prospective cohort study. (ClinicalTrials.gov: NCT01755052). Setting: 94 hospitals throughout the United States. Participants: 3006 persons aged 75 years or older who were hospitalized with AMI and discharged alive. Measurements: Functional impairments were assessed during hospitalization via direct measurement (cognition, mobility, muscle strength) or self-report (vision, hearing). Clinical variables associated with mortality in prior risk models were ascertained by chart review. Seventy-two candidate variables were selected for inclusion, and backward selection and Bayesian model averaging were used to derive (n = 2004 participants) and validate (n = 1002 participants) a model for 6-month mortality. Results: Participants' mean age was 81.5 years, 44.4% were women, and 10.5% were nonwhite. There were 266 deaths (8.8%) within 6 months. The final risk model included 15 variables, 4 of which were not included in prior risk models: hearing impairment, mobility impairment, weight loss, and lower patient-reported health status. The model was well calibrated (Hosmer-Lemeshow P > 0.05) and showed good discrimination (area under the curve for the validation cohort = 0.84). Adding functional impairments significantly improved model performance, as evidenced by category-free net reclassification improvement indices of 0.21 (P = 0.008) for hearing impairment and 0.26 (P < 0.001) for mobility impairment. Limitation: The model was not externally validated. Conclusion: A newly developed model for 6-month post-AMI mortality in older adults was well calibrated and had good discriminatory ability. This model may be useful in decision making at hospital discharge. Primary Funding Source: National Heart, Lung, and Blood Institute of the National Institutes of Health.

Multiple network-constrained regressions expand insights into influenza vaccination responses.

MOTIVATION: Systems immunology leverages recent technological advancements that enable broad profiling of the immune system to better understand the response to infection and vaccination, as well as the dysregulation that occurs in disease. An increasingly common approach to gain insights from these large-scale profiling experiments involves the application of statistical learning methods to predict disease states or the immune response to perturbations. However, the goal of many systems studies is not to maximize accuracy, but rather to gain biological insights. The predictors identified using current approaches can be biologically uninterpretable or present only one of many equally predictive models, leading to a narrow understanding of the underlying biology. RESULTS: Here we show that incorporating prior biological knowledge within a logistic modeling framework by using network-level constraints on transcriptional profiling data significantly improves interpretability. Moreover, incorporating different types of biological knowledge produces models that highlight distinct aspects of the underlying biology, while maintaining predictive accuracy. We propose a new framework, Logistic Multiple Network-constrained Regression (LogMiNeR), and apply it to understand the mechanisms underlying differential responses to influenza vaccination. Although standard logistic regression approaches were predictive, they were minimally interpretable. Incorporating prior knowledge using LogMiNeR led to models that were equally predictive yet highly interpretable. In this context, B cell-specific genes and mTOR signaling were associated with an effective vaccination response in young adults. Overall, our results demonstrate a new paradigm for analyzing high-dimensional immune profiling data in which multiple networks encoding prior knowledge are incorporated to improve model interpretability. AVAILABILITY AND IMPLEMENTATION: The R source code described in this article is publicly available at https://bitbucket.org/kleinstein/logminer . CONTACT: steven.kleinstein@yale.edu or stefan.avey@yale.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Prolonged proinflammatory cytokine production in monocytes modulated by interleukin 10 after influenza vaccination in older adults.

We evaluated in vivo innate immune responses in monocyte populations from 67 young (aged 21-30 years) and older (aged ≥65 years) adults before and after influenza vaccination. CD14(+)CD16(+) inflammatory monocytes were induced after vaccination in both young and older adults. In classical CD14(+)CD16(-) and inflammatory monocytes, production of tumor necrosis factor α and interleukin 6, as measured by intracellular staining, was strongly induced after vaccination. Cytokine production was strongly associated with influenza vaccine antibody response; the highest levels were found as late as day 28 after vaccination in young subjects and were substantially diminished in older subjects. Notably, levels of the anti-inflammatory cytokine interleukin 10 (IL-10) were markedly elevated in monocytes from older subjects before and after vaccination. In purified monocytes, we found age-associated elevation in phosphorylated signal transducer and activator of transcription-3, and decreased serine 359 phosphorylation of the negative IL-10 regulator dual-specificity phosphatase 1. These findings for the first time implicate dysregulated IL-10 production in impaired vaccine responses in older adults.

Design and rationale of the comprehensive evaluation of risk factors in older patients with AMI (SILVER-AMI) study.

BACKGROUND: While older adults (age 75 and over) represent a large and growing proportion of patients with acute myocardial infarction (AMI), they have traditionally been under-represented in cardiovascular studies. Although chronological age confers an increased risk for adverse outcomes, our current understanding of the heterogeneity of this risk is limited. The Comprehensive Evaluation of Risk Factors in Older Patients with AMI (SILVER-AMI) study was designed to address this gap in knowledge by evaluating risk factors (including geriatric impairments, such as muscle weakness and cognitive impairments) for hospital readmission, mortality, and health status decline among older adults hospitalized for AMI. METHODS/DESIGN: SILVER-AMI is a prospective cohort study that is enrolling 3000 older adults hospitalized for AMI from a recruitment network of approximately 70 community and academic hospitals across the United States. Participants undergo a comprehensive in-hospital assessment that includes clinical characteristics, geriatric impairments, and health status measures. Detailed medical record abstraction complements the assessment with diagnostic study results, in-hospital procedures, and medications. Participants are subsequently followed for six months to determine hospital readmission, mortality, and health status decline. Multivariable regression will be used to develop risk models for these three outcomes. DISCUSSION: SILVER-AMI will fill critical gaps in our understanding of AMI in older patients. By incorporating geriatric impairments into our understanding of post-AMI outcomes, we aim to create a more personalized assessment of risk and identify potential targets for interventions. TRIAL REGISTRATION NUMBER: NCT01755052 .

Investigating brain dynamics and their association with cognitive control in opioid use disorder using naturalistic and drug cue paradigms.

Objectives: Opioid use disorder (OUD) impacts millions of people worldwide. The prevalence and debilitating effects of OUD present a pressing need to understand its neural mechanisms to provide more targeted interventions. Prior studies have linked altered functioning in large-scale brain networks with clinical symptoms and outcomes in OUD. However, these investigations often do not consider how brain responses change over time. Time-varying brain network engagement can convey clinically relevant information not captured by static brain measures. Methods: We investigated brain dynamic alterations in individuals with OUD by applying a new multivariate computational framework to movie-watching (i.e., naturalistic; N=76) and task-based (N=70) fMRI. We further probed the associations between cognitive control and brain dynamics during a separate drug cue paradigm in individuals with OUD. Results: Compared to healthy controls (N=97), individuals with OUD showed decreased variability in the engagement of recurring brain states during movie-watching. We also found that worse cognitive control was linked to decreased variability during the rest period when no opioid-related stimuli were present. Conclusions: These findings suggest that individuals with OUD may experience greater difficulty in effectively engaging brain networks in response to evolving internal or external demands. Such inflexibility may contribute to aberrant response inhibition and biased attention toward opioid-related stimuli, two hallmark characteristics of OUD. By incorporating temporal information, the current study introduces novel information about how brain dynamics are altered in individuals with OUD and their behavioral implications.

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

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

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

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

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

Dectin-1 stimulation promotes a distinct inflammatory signature in the setting of HIV-infection and aging.

Dectin-1 is an innate immune receptor that recognizes and binds ß-1, 3/1, 6 glucans on fungi. We evaluated Dectin-1 function in myeloid cells in a cohort of HIV-positive and HIV-negative young and older adults. Stimulation of monocytes with ß-D-glucans induced a pro-inflammatory phenotype in monocytes of HIV-infected individuals that was characterized by increased levels of IL-12, TNF-α, and IL-6, with some age-associated cytokine increases also noted. Dendritic cells showed a striking HIV-associated increase in IFN-α production. These increases in cytokine production paralleled increases in Dectin-1 surface expression in both monocytes and dendritic cells that were noted with both HIV and aging. Differential gene expression analysis showed that HIV-positive older adults had a distinct gene signature compared to other cohorts characterized by a robust TNF-α and coagulation response (increased at baseline), a persistent IFN-α and IFN-γ response, and an activated dendritic cell signature/M1 macrophage signature upon Dectin-1 stimulation. Dectin-1 stimulation induced a strong upregulation of MTORC1 signaling in all cohorts, although increased in the HIV-Older cohort (stimulation and baseline). Overall, our study demonstrates that the HIV Aging population has a distinct immune signature in response to Dectin-1 stimulation. This signature may contribute to the pro-inflammatory environment that is associated with HIV and aging.

Platelet response to influenza vaccination reflects effects of aging.

Platelets are uniquely positioned as mediators of not only hemostasis but also innate immunity. However, how age and geriatric conditions such as frailty influence platelet function during an immune response remains unclear. We assessed the platelet transcriptome at baseline and following influenza vaccination in Younger (age 21-35) and Older (age ≥65) adults (including community-dwelling individuals who were largely non-frail and skilled nursing facility (SNF)-resident adults who nearly all met criteria for frailty). Prior to vaccination, we observed an age-associated increase in the expression of platelet activation and mitochondrial RNAs and decrease in RNAs encoding proteins mediating translation. Age-associated differences were also identified in post-vaccination response trajectories over 28 days. Using tensor decomposition analysis, we found increasing RNA expression of genes in platelet activation pathways in young participants, but decreasing levels in (SNF)-resident adults. Translation RNA trajectories were inversely correlated with these activation pathways. Enhanced platelet activation was found in community-dwelling older adults at the protein level, compared to young individuals both prior to and post-vaccination; whereas SNF residents showed decreased platelet activation compared to community-dwelling older adults that could reflect the influence of decreased translation RNA expression. Our results reveal alterations in the platelet transcriptome and activation responses that may contribute to age-associated chronic inflammation and the increased incidence of thrombotic and pro-inflammatory diseases in older adults.

Factors Associated With Cardiac Rehabilitation Participation in Older Adults After Myocardial Infarction: THE SILVER-AMI STUDY.

PURPOSE: Cardiac rehabilitation (CR) is a key aspect of secondary prevention following acute myocardial infarction (AMI). While there is growing evidence of unique benefits of CR in older adults, it remains underutilized. We aimed to examine specific demographic, clinical, and functional factors associated with utilization of CR among older adults hospitalized with AMI. METHODS: Our project used data from the SILVER-AMI study, a nationwide prospective cohort study of patients age ≥75 yr hospitalized with AMI and followed them up for 6 mo after discharge. Extensive baseline data were collected on demographics, clinical and psychosocial factors, and functional and sensory impairments. The utilization of CR was collected by a survey at 6 mo. Backward selection was employed in a multivariable-adjusted logistic regression model to identify independent predictors of CR use. RESULTS: Of the 2003 participants included in this analysis, 779 (39%) reported participating in CR within 6 mo of discharge. Older age, longer length of hospitalization, having ≤12 yr of education, visual impairment, cognitive impairment, and living alone were associated with decreased likelihood of CR participation; receipt of diagnostic and interventional procedures (ie, cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft) was associated with increased likelihood of CR participation. CONCLUSIONS: Demographic and clinical factors, as well as select functional and sensory impairments common in aging, were associated with CR participation at 6 mo post-discharge in older AMI patients. These results highlight opportunities to increase CR usage among older adults and identify those at risk for not participating.

Strong cardiovascular prognostic implication of quantitative left atrial contractile function assessed by cardiac magnetic resonance imaging in patients with chronic hypertension.

BACKGROUND: Progressive left ventricular (LV) diastolic dysfunction due to hypertension (HTN) alters left atrial (LA) contractile function in a predictable manner. While increased LA size is a marker of LV diastolic dysfunction and has been shown to be predictive of adverse cardiovascular outcomes, the prognostic significance of altered LA contractile function is unknown. METHODS: A consecutive group of patients with chronic hypertension but without significant valvular disease or prior MI underwent clinically-indicated CMR for assessment of left ventricular (LV) function, myocardial ischemia, or viability. Calculation of LA volumes used in determining LA emptying functions was performed using the biplane area-length method. RESULTS: Two-hundred and ten patients were included in this study. During a median follow-up of 19 months, 48 patients experienced major adverse cardiac events (MACE), including 24 deaths. Decreased LA contractile function (LAEF(Contractile)) demonstrated strong unadjusted associations with patient mortality, non-fatal events, and all MACE. For every 10% reduction of LAEF(Contractile), unadjusted hazards to MACE, all-cause mortality, and non-fatal events increased by 1.8, 1.5, and 1.4-folds, respectively. In addition, preservation of the proportional contribution from LA contraction to total diastolic filling (Contractile/Total ratio) was strongly associated with lower MACE and patient mortality. By multivariable analyses, LAEF(Contractile) was the strongest predictor in each of the best overall models of MACE, all-cause mortality, and non-fatal events. Even after adjustment for age, gender, left atrial volume, and LVEF, LAEF(Contractile) maintained strong independent associations with MACE (p < 0.0004), all-cause mortality (p < 0.0004), and non-fatal events (p < 0.0004). CONCLUSIONS: In hypertensive patients at risk for left ventricular diastolic dysfunction, a decreased contribution of LA contractile function to ventricular filling during diastole is strongly predictive of adverse cardiac events and death.

The association of neighborhood walkability with health outcomes in older adults after acute myocardial infarction: The SILVER-AMI study.

Physical activity and social support are associated with better outcomes after surviving acute myocardial infarction (AMI), and greater walkability has been associated with activity and support. We used data from the SILVER-AMI study (November 2014-June 2017), a longitudinal cohort of community-living adults ≥ 75 years hospitalized for AMI to assess associations of neighborhood walkability with health outcomes, and to assess whether physical activity and social support mediate this relationship, if it exists. We included data from 1345 participants who were not bedbound, were discharged home, and for whom we successfully linked walkability scores (from Walk Score®) for their home census block. Our primary outcome was hospital-free survival time (HFST) at six months after discharge; secondary outcomes included physical and mental health at six months, assessed using SF-12. Physical activity and social support were measured at baseline. Covariates included cognition, functioning, comorbidities, participation in rehabilitation or physical therapy, and demographics. We employed survival analysis to examine associations between walkability and HFST, before and after adjustment for covariates; we repeated analyses using linear regression with physical and mental health as outcomes. In adjusted models, walkability was not associated with physical health (ß = 0.010; 95% CI: -0.027, 0.047), mental health (ß = -0.08; 95% CI: -0.175, -0.013), or HFST (ß = 0.008; 95% CI: -0.023, 0.009). Social support was associated with mental health in adjusted models. Neighborhood walkability was not predictive of outcomes among older adults with existing coronary disease, suggesting that among older adults, mobility limitations may supercede neighborhood walkability.

Presentation, Treatment, and Outcomes of the Oldest-Old Patients with Acute Myocardial Infarction: The SILVER-AMI Study.

BACKGROUND: Oldest-old patients (≥85 years) constitute half the acute myocardial infarction hospitalizations among older adults and more commonly have atypical presentation, under-treatment, and functional impairments. Yet this group has not been well characterized. We characterized differences in presentation, functional impairments, treatments, health status, and mortality among middle-old (75-84 years) and oldest-old patients with myocardial infarction. METHODS: We analyzed data from the ComprehenSIVe Evaluation of Risk Factors in Older Patients with AMI (SILVER-AMI) study that enrolled 3041 patients ≥75 years of age from 94 hospitals across the US between 2013 and 2016. We performed Cox proportional hazards regression to examine the association between the oldest-old (n = 831) and middle-old (n = 2210) age categories with postdischarge 6-month case fatality rate adjusting for sociodemographic and clinical variables, and mobility impairment. RESULTS: The oldest-old were less likely to present with chest pain (52.7% vs 57.7%) as their primary symptom or to receive coronary revascularization (58.1% vs 71.8) (P < .01 for both). The oldest-old were more likely to have functional impairments and had higher 6-month mortality compared with the middle-old patients (hazard ratio 1.78, 95% confidence interval, 1.39-2.28). This association was substantially attenuated after adjusting for mobility impairment (hazard ratio 1.29, confidence interval, 0.99-1.68). CONCLUSIONS: There is considerable heterogeneity in presentation, treatment, and outcomes among older patients with myocardial infarction. Mobility impairment, a marker for frailty, modifies the association between advanced age and treatments as well as outcomes.

Presentation, Treatment, and Outcomes of Older Adults Hospitalized for Acute Myocardial Infarction According to Cognitive Status: The SILVER-AMI Study.

BACKGROUND: While survival after acute myocardial infarction has improved substantially, older adults remain at heightened risk for hospital readmissions and death. Evidence for the role of cognitive impairment in older myocardial infarction survivors' risk for these outcomes is limited. METHODS: 3041 patients aged ≥75 years hospitalized with acute myocardial infarction (mean age 82 ± 5 years, 56% male) recruited from 94 US hospitals. Cognition was assessed using the Telephone Interview for Cognitive Status; scores of <27 and <22 indicated mild and moderate/severe impairment, respectively. Readmissions and death at 6 months post-discharge were ascertained via participant report and medical record review. Associations between cognition and outcomes were evaluated with multivariable-adjusted logistic regression. RESULTS: Mild and moderate/severe cognitive impairment were present in 11% and 6% of the cohort, respectively. Readmission and death at 6 months occurred in 41% and 9% of participants, respectively. Mild and moderate/severe cognitive impairment were associated with increased risk of readmission (odds ratio [OR] 1.36; 95% confidence interval [CI], 1.08-1.72 and OR 1.58; 95% CI, 1.18-2.12, respectively) and death (OR 2.19; 95% CI, 1.54-3.11 and OR 3.82; 95% CI, 2.63-5.56, respectively) in unadjusted analyses. Significant associations between moderate/severe cognitive impairment and death (OR 1.69; 95% CI, 1.10-2.59) persisted after adjustment for demographics, myocardial infarction characteristics, comorbidity burden, functional status, and depression, but not for readmissions. CONCLUSIONS: Moderate-to-severe cognitive impairment is associated with heightened risk of death in older acute myocardial infarction patients in the months after hospitalization, but not with readmission. Routine cognitive screening may identify older myocardial infarction survivors at risk for poor outcomes who may benefit from closer oversight and support in the post-discharge period.

Falls in older adults after hospitalization for acute myocardial infarction.

BACKGROUND: After hospitalization for acute myocardial infarction (AMI), older adults may be at increased risk for falls due to deconditioning, new medications, and worsening health status. Our primary objective was to identify risk factors for falls after AMI hospitalization among adults over age 75. METHODS: We used data from the Comprehensive Evaluation of Risk Factors in Older Patients with AMI (SILVER-AMI) study, a prospective cohort study of 3041 adults age 75 and older hospitalized with AMI at 94 community and academic medical centers across the United States. In-person interviews and physical assessments, as well as medical record review, were performed to collect demographic, clinical, functional, and psychosocial data. Falls were self-reported in telephone interviews and medically serious falls (those associated with emergency department use or hospitalization) were determined by medical record adjudication. Backward selection was used to identify predictors of fall risk in logistic regression analysis. RESULTS: A total of 554 (21.6%) participants reported a fall and 191 (6.4%) had a medically serious fall within 6 months of discharge. Factors independently associated with self-reported falls included impaired mobility, prior fall history, longer hospital stay, visual impairment, and weak grip. Factors independently associated with medically serious falls included older age, polypharmacy, impaired functional mobility, prior fall history, and living alone. CONCLUSIONS: Among older patients hospitalized for AMI, falls are common in the 6 months following discharge and associated with demographic, functional, and clinical factors that are readily identifiable. Fall risk should be considered in post-AMI clinical decision-making and interventions to prevent falls should be evaluated.

Development and Validation of a Risk Prediction Model for 1-Year Readmission Among Young Adults Hospitalized for Acute Myocardial Infarction.

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.

180-day readmission risk model for older adults with acute myocardial infarction: the SILVER-AMI study.

OBJECTIVE: To develop a 180-day readmission risk model for older adults with acute myocardial infarction (AMI) that considered a broad range of clinical, demographic and age-related functional domains. METHODS: We used data from ComprehenSIVe Evaluation of Risk in Older Adults with AMI (SILVER-AMI), a prospective cohort study that enrolled participants aged ≥75 years with AMI from 94 US hospitals. Participants underwent an in-hospital assessment of functional impairments, including cognition, vision, hearing and mobility. Clinical variables previously shown to be associated with readmission risk were also evaluated. The outcome was 180-day readmission. From an initial list of 72 variables, we used backward selection and Bayesian model averaging to derive a risk model (N=2004) that was subsequently internally validated (N=1002). RESULTS: Of the 3006 SILVER-AMI participants discharged alive, mean age was 81.5 years, 44.4% were women and 10.5% were non-white. Within 180 days, 1222 participants (40.7%) were readmitted. The final risk model included 10 variables: history of chronic obstructive pulmonary disease, history of heart failure, initial heart rate, first diastolic blood pressure, ischaemic ECG changes, initial haemoglobin, ejection fraction, length of stay, self-reported health status and functional mobility. Model discrimination was moderate (0.68 derivation cohort, 0.65 validation cohort), with good calibration. The predicted readmission rate (derivation cohort) was 23.0% in the lowest quintile and 65.4% in the highest quintile. CONCLUSIONS: Over 40% of participants in our sample experienced hospital readmission within 180 days of AMI. Our final readmission risk model included a broad range of characteristics, including functional mobility and self-reported health status, neither of which have been previously considered in 180-day risk models.

Patient expectations from implantable defibrillators to prevent death in heart failure.

BACKGROUND: Indications for implantable cardioverter-defibrillators (ICDs) in heart failure (HF) are expanding and may include more than 1 million patients. This study examined patient expectations from ICDs for primary prevention of sudden death in HF. METHODS AND RESULTS: Study participants (n = 105) had an EF <35% and symptomatic HF, without history of ventricular tachycardia/fibrillation or syncope. Subjects completed a written survey about perceived ICD benefits, survival expectations, and circumstances under which they might deactivate defibrillation. Mean age was 58, LVEF 21%, 40% were New York Heart Association Class III-IV, and 65% already had a primary prevention ICD. Most patients anticipated more than10 years survival despite symptomatic HF. Nearly 54% expected an ICD to save >or=50 lives per 100 during 5 years. ICD recipients expressed more confidence that the device would save their own lives compared with those without an ICD (P < .001). Despite understanding the ease of deactivation, 70% of ICD recipients indicated they would keep the ICD on even if dying of cancer, 55% even if having daily shocks, and none would inactivate defibrillation even if suffering constant dyspnea at rest. CONCLUSIONS: HF patients anticipate long survival, overestimate survival benefits conferred by ICDs, and express reluctance to deactivate their devices even for end-stage disease.

Comorbid vision and cognitive impairments in older adults hospitalized for acute myocardial infarction.

Older patients presenting with acute myocardial infarction (AMI) often have comorbidities. Our objective was to examine how outcomes differ by cognitive and vision status in older AMI patients. We use data from a prospective cohort study conducted at 94 hospitals in the United States between January 2013 and October 2016 that enrolled men and women aged ≥75 years with AMI. Cognitive impairment (CI) was defined as telephone interview for cognitive status (TICS) score <27; vision impairment (VI) and activities of daily living (ADLs) were assessed by questionnaire. Of 2988 senior AMI patients, 260 (8.7%) had CI but no VI, 858 (28.7%) had VI but no CI, and 251 (8.4%) had both CI/VI. Patients in the VI/CI group were most likely to exhibit geriatric syndromes. More severe VI was associated with lower (worse) scores on the TICS (ß -1.53, 95% confidence interval (CI) -1.87 to -1.18). In adjusted models, compared to participants with neither impairment, participants with VI/CI were more likely to die (hazard ratio 1.61, 95% CI 1.10-2.37) and experience ADL decline (odds ratio 2.11, 95% CI 1.39-3.21) at 180 days. Comorbid CIs and VIs were associated with high rates of death and worsening disability after discharge among seniors hospitalized for AMI. Future research should evaluate protocols to accommodate these impairments during AMI presentations and optimize decision-making and outcomes.