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Background: Associations between magnetic resonance imaging markers of cerebral small vessel disease (CSVD) and dementia risk in older adults have been established, but it remains unclear how lifestyle factors, including psychosocial health, may modify this association., Methods: Social support and social isolation were assessed among participants of the community-based ARIC (Atherosclerosis Risk in Communities) Study, via self-reported questionnaires (1990-1992). Following categorization of both factors, participants were classified as having strong or poor mid-life social relationships. At visit 5 (2011-2013), participants underwent 3T brain magnetic resonance imaging quantifying CSVD measures: white matter hyperintensity volume, microbleeds (subcortical), infarcts (lacunar), and white matter integrity (diffusion tensor imaging). Incident dementia cases were identified from the time of imaging through December 31, 2020 with ongoing surveillance. Associations between CSVD magnetic resonance imaging markers and incident dementia were evaluated using Cox proportional-hazard regressions adjusted for demographic and additional risk factors (from visit 2). Effect modification by mid-life social relationships was evaluated., Results: Of the 1977 participants with magnetic resonance imaging, 1617 participants (60.7% women; 26.5% Black participants; mean age at visit 2, 55.4 years) were examined. In this sample, mid-life social relationships significantly modified the association between white matter hyperintensity volume and dementia risk ( P interaction=0.001). Greater white matter hyperintensity volume was significantly associated with risk of dementia in all participants, yet, more substantially in those with poor (hazard ratio, 1.84 [95% CI, 1.49-2.27]) versus strong (hazard ratio, 1.26 [95% CI, 1.08-1.47]) mid-life social relationships. Although not statistically significant, subcortical microbleeds in participants with poor mid-life social relationships were associated with a greater risk of dementia, relative to those with strong social relationships, in whom subcortical microbleeds were no longer associated with elevated dementia risk., Conclusions: The elevated risk of dementia associated with CSVD may be reduced in participants with strong mid-life social relationships. Future studies evaluating psychosocial health through the life course and the mechanisms by which they modify the relationship between CSVD and dementia are needed., Competing Interests: Dr Knopman serves on a Data Safety Monitoring Board for the Dominantly Inherited Alzheimer Network Treatment Unit study. He is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the University of Southern California. He has served as a consultant for Roche, Samus Therapeutics, Magellan Health, Biovie, and Alzeca Biosciences but receives no personal compensation. He attended an Eisai advisory board meeting for lecanemab on December 2, 2022 but received no compensation directly or indirectly. He receives funding from the NIH and grants from Washington University School of Medicine in St. Louis. Dr Lutsey reports grants from the National Institutes of Health (NIH) to her institution. Dr Mosley is supported by NIH/National Heart, Lung, and Blood Institute (NHLBI) 75N92022D0004 and NIH/NHLBI: U01HL096812. Dr Palta is supported by NIH/NHLBI 75N92022D00005. Dr Walker is supported by the National Institute on Aging’s Intramural Research Program (AG000348-01, AG000349-01). Dr Gottesman served on the American Neurological Association as program chair from 2021 to 2023 and received no personal compensation. The other authors report no conflicts.

Importance: Hearing loss may contribute to poor functional status via cognitive impairment and social isolation. Hearing aids may play a protective role by attenuating these downstream outcomes. However, population-based evidence is lacking., Objective: To examine the association of hearing loss and hearing aids with functional status., Design, Setting, and Participants: This cross-sectional (2016-2017) and longitudinal (2016-2022) analysis of data from the Atherosclerosis Risk in Communities cohort study included older, community-dwelling adults with complete data. Data were analyzed from June to December 2023., Exposures: The better-hearing ear's pure tone average (BPTA) at speech frequencies (0.5-4 kHz) was modeled categorically (no [BPTA ≤25 dB], mild [26-40 dB], and moderate or greater hearing loss [>40 dB]). Hearing aid use was self-reported., Main Outcomes and Measures: Difficulties in activities of daily living (ADLs; eg, dressing and eating), instrumental activities of daily living (IADLS; eg, household chores and meal preparation), and heavier tasks (eg, walking a quarter of a mile) were self-reported at visit 6. The ability to perform usual activities, walk a half mile, walk up and down stairs, and do heavy housework without help were collected in follow-up surveys. Linear and logistic regression models were used that were adjusted for sociodemographic and health covariates., Results: Among 3142 participants (mean [SD] age, 79.3 [4.6] years; 1828 women [58.2%]), 1013 (32.2%) had no hearing loss, 1220 (38.8%) had mild hearing loss, and 909 (29.0%) had moderate or greater hearing loss. Moderate or greater hearing loss was cross-sectionally associated with difficulty in 1 or more ADLs (odds ratio [OR], 1.27; 95% CI, 1.02-1.58), IADLs (OR, 1.34; 95% CI, 1.05-1.71), and heavier tasks (OR, 1.29; 95% CI, 1.04-1.62) compared with no hearing loss. Over time (mean [SD] follow-up, 1.9 [1.8] years), moderate or greater hearing loss was associated with a faster decline in the number of activities participants were able to do (β = -0.07 per year; 95% CI, -0.09 to -0.06) and greater odds of reporting inability to do 1 or more of the 4 activities (OR, 1.14; 95% CI, 1.05-1.24). Hearing aid users and nonusers did not differ., Conclusions and Relevance: The results of this study suggest that moderate or greater hearing loss was associated with functional difficulties and may contribute to a faster decline in function longitudinally independent of sociodemographic and health covariates. Hearing aids did not change the association among those with hearing loss.

Importance: There are consistent data demonstrating that socioeconomic disadvantage is associated with risk of premature mortality, but research on the relationship between neighborhood socioeconomic factors and premature mortality is limited. Most studies evaluating the association between neighborhood socioeconomic status (SES) and mortality have used a single assessment of SES during middle to older adulthood, thereby not considering the contribution of early life neighborhood SES., Objective: To investigate the association of life course neighborhood SES and premature mortality., Design, Setting, and Participants: This cohort study included Black and White participants of the multicenter Atherosclerosis Risk in Communities Study, a multicenter study conducted in 4 US communities: Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the northwestern suburbs of Minneapolis, Minnesota. Participants were followed up for a mean (SD) of 18.8 (5.7) years (1996-2020). Statistical analysis was performed from March 2023 through May 2024., Exposure: Participants' residential addresses during childhood, young adulthood, and middle adulthood were linked with US Census-based socioeconomic indicators to create summary neighborhood SES scores for each of these life epochs. Neighborhood SES scores were categorized into distribution-based tertiles., Main Outcomes and Measures: Premature death was defined as all-cause mortality occurring before age 75 years. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs., Results: Among 12 610 study participants, the mean (SD) age at baseline was 62.6 (5.6) years; 3181 (25.2%) were Black and 9429 (74.8%) were White; and 7222 (57.3%) were women. The lowest, compared with the highest tertile, of neighborhood SES score in middle adulthood was associated with higher risk of premature mortality (HR, 1.28; 95% CI, 1.07-1.54). Similar associations were observed for neighborhood SES in young adulthood among women (HR, 1.25; 95% CI, 1.00-1.56) and neighborhood SES in childhood among White participants (HR, 1.25; 95% CI, 1.01-1.56). Participants whose neighborhood SES remained low from young to middle adulthood had an increased premature mortality risk compared with those whose neighborhood SES remained high (HR, 1.25; 95% CI, 1.05-1.49)., Conclusions and Relevance: In this study, low neighborhood SES was associated with premature mortality. The risk of premature mortality was greatest among individuals experiencing persistently low neighborhood SES from young to middle adulthood. Place-based interventions that target neighborhood social determinants of health should be designed from a life course perspective that accounts for early-life socioeconomic inequality.

Background: Self-rated health is a simple measure that may identify individuals who are at a higher risk for hospitalization or death., Objective: To quantify the association between a single measure of self-rated health and future risk of recurrent hospitalizations or death., Participants: Atherosclerosis Risk in Communities (ARIC) study, a community-based prospective cohort study of middle-aged men and women with follow-up beginning from 1987 to 1989., Main Measures: We quantified the associations between initial self-rated health with risk of recurrent hospitalizations and of death using a recurrent events survival model that allowed for dependency between the rates of hospitalization and hazards of death, adjusted for demographic and clinical factors., Key Results: Of the 14,937 ARIC cohort individuals with available self-rated health and covariate information, 34% of individuals reported "excellent" health, 47% "good," 16% "fair," and 3% "poor" at study baseline. After a median follow-up of 27.7 years, 1955 (39%), 3569 (51%), 1626 (67%), and 402 (83%) individuals with "excellent," "good," "fair," and "poor" health, respectively, had died. After adjusting for demographic factors and medical history, a less favorable self-rated health status was associated with increased rates of hospitalization and death. As compared to those reporting "excellent" health, adults with "good," "fair," and "poor" health had 1.22 (1.07 to 1.40), 2.01 (1.63 to 2.47), and 3.13 (2.39 to 4.09) times the rate of hospitalizations, respectively. The hazards of death also increased with worsening categories of self-rated health, with "good," "fair," and "poor" health individuals experiencing 1.30 (1.12 to 1.51), 2.15 (1.71 to 2.69), and 3.40 (2.54 to 4.56) times the hazard of death compared to "excellent," respectively., Conclusions: Even after adjusting for demographic and clinical factors, having a less favorable response on a single measure of self-rated health taken in middle age is a potent marker of future hospitalizations and death., (© 2024. The Author(s).)

Importance: Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden., Objective: To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days., Design, Setting, and Participants: For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection., Exposure: Preinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires., Main Outcomes and Measures: Probability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days., Results: Of 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections., Conclusions and Relevance: In this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.

Introduction: This study aimed to assess whether social relationships in mid-life reduce the risk of dementia related to amyloid burden., Methods: Participants in the Atherosclerosis Risk in Communities (ARIC) study were assessed for social support and isolation (visit 2; 1990-1992). A composite measure, "social relationships," was generated. Brain amyloid was evaluated with florbetapir positron emission tomography (PET); (visit 5; 2012-2014). Incident dementia cases were identified following visit 5 through 2019 using ongoing surveillance. Relative contributions of mid-life social relationships and elevated brain amyloid to incident dementia were evaluated with Cox regression models., Results: Among 310 participants without dementia, strong mid-life social relationships were associated independently with lower dementia risk. Elevated late-life brain amyloid was associated with greater dementia risk., Discussion: Although mid-life social relationships did not moderate the relationship between amyloid burden and dementia, these findings affirm the importance of strong social relationships as a potentially protective factor against dementia., Competing Interests: Renée C. Groechel, Albert C. Liu, Chelsea Liu, Silvia Koton, Anna M. Kucharska‐Newton, Pamela L. Lutsey, Thomas H. Mosley Jr., Priya Palta, A. Richey Sharrett, Keenan A. Walker, Dean F. Wong, Rebecca F. Gottesman: no conflicts to report. David S. Knopman: serves on a data safety monitoring board for the Dominantly Inherited Alzheimer Network Treatment Unit study. He served on a data safety monitoring board for a tau therapeutic for Biogen (until 2021) but received no personal compensation. He is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the University of Southern California. He has served as a consultant for Roche, Samus Therapeutics, Magellan Health, Biovie, and Alzeca Biosciences but receives no personal compensation. He attended an Eisai advisory board meeting for lecanemab in December 2, 2022, but received no compensation directly or indirectly. He receives funding from the NIH. Author disclosures are available in the Supporting Information., (© 2024 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objectives: To examine the association of prestroke continuity of care (COC) with postdischarge health care utilization and expenditures., Study Population: The study population included 2233 patients with a diagnosis of stroke or a transient ischemic attack hospitalized in one of 41 hospitals in North Carolina between March 2016 and July 2019 and discharged directly home from acute care., Methods: COC was assessed from linked Centers for Medicare and Medicaid Services Medicare claims using the Modified, Modified Continuity Index. Logistic regressions and 2-part models were used to examine the association of prestroke primary care COC with postdischarge health care utilization and expenditures., Results: Relative to patients in the first (lowest) COC quartile, patients in the second and third COC quartiles were more likely [21% (95% CI: 8.5%, 33.5%) and 33% (95% CI: 20.5%, 46.1%), respectively] to have an ambulatory care visit within 14 days. Patients in the highest COC quartile were more likely to visit a primary care provider but less likely to see a stroke specialist. Highest as compared with lowest primary care COC quartile was associated with $45 lower (95% CI: $14, $76) average expenditure for ambulatory care visits within 30 days postdischarge. Patients in the highest, as compared with the lowest, primary care COC quartile were 36% less likely (95% CI: 8%, 64%) to be readmitted within 30 days postdischarge and spent $340 less (95% CI: $2, $678) on unplanned readmissions., Conclusions: These findings underscore the importance of primary care COC received before stroke hospitalization to postdischarge care and expenditures., Competing Interests: P.D. and C.B.: Ownership in Care Directions, LLC. The remaining authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine the association between brain MRI abnormalities and incident epilepsy in older adults., Methods: Men and women (ages 45-64 years) from the Atherosclerosis Risk in Communities study were followed up from 1987 to 2018 with brain MRI performed between 2011 and 2013. We identified cases of incident late-onset epilepsy (LOE) with onset of seizures occurring after the acquisition of brain MRI. We evaluated the relative pattern of cortical thickness, subcortical volume, and white matter integrity among participants with incident LOE after MRI in comparison with participants without seizures. We examined the association between MRI abnormalities and incident LOE using Cox proportional hazards regression. Models were adjusted for demographics, hypertension, diabetes, smoking, stroke, and dementia status., Results: Among 1251 participants with brain MRI data, 27 (2.2%) developed LOE after MRI over a median of 6.4 years (25-75 percentile 5.8-6.9) of follow-up. Participants with incident LOE after MRI had higher levels of cortical thinning and white matter microstructural abnormalities before seizure onset compared to those without seizures. In longitudinal analyses, greater number of abnormalities was associated with incident LOE after controlling for demographic factors, risk factors for cardiovascular disease, stroke, and dementia (gray matter: hazard ratio [HR]: 2.3, 95% confidence interval [CI]: 1.0-4.9; white matter diffusivity: HR: 3.0, 95% CI: 1.2-7.3)., Interpretation: This study demonstrates considerable gray and white matter pathology among individuals with LOE, which is present prior to the onset of seizures and provides important insights into the role of neurodegeneration, both of gray and white matter, and the risk of LOE., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Introduction: We examined the association of both midlife occupation and age at retirement with cognitive decline in the Atherosclerosis Risk in Communities (ARIC) biracial community-based cohort., Methods: Current or most recent occupation at ARIC baseline (1987-1989; aged 45-64 years) was categorized based on 1980 US Census major occupation groups and tertiles of the Nam-Powers-Boyd occupational status score (n = 14,090). Retirement status via annual follow-up questionnaires administered ascertained in 1999-2007 was classified as occurring before or after age 70 (n = 7,503). Generalized estimating equation models were used to examine associations of occupation and age at retirement with trajectories of global cognitive factor scores, assessed from visit 2 (1990-1992) to visit 5 (2011-2013). Models were a priori stratified by race and sex and adjusted for demographics and comorbidities., Results: Low occupational status and blue-collar occupations were associated with low baseline cognitive scores in all race-sex strata. Low occupational status and homemaker status were associated with faster decline in white women but slower decline in black women compared to high occupational status. Retirement before age 70 was associated with slower cognitive decline in white men and women and in black men. Results did not change substantially after accounting for attrition., Conclusion: Low occupational status was associated with cognitive decline in women but not in men. Earlier retirement was associated with a slower cognitive decline in white participants and in black men. Further research should explore reasons for the observed associations and race-sex differences., (© 2024 S. Karger AG, Basel.)

Background: Psychosocial factors are modifiable risk factors for Alzheimer's disease (AD). One mechanism linking psychosocial factors to AD risk may be through biological measures of brain amyloid; however, this association has not been widely studied., Objective: To determine if mid-life measures of social support and social isolation in the Atherosclerosis Risk in Communities (ARIC) Study cohort are associated with late life brain amyloid burden, measured using florbetapir positron emission tomography (PET)., Methods: Measures of social support and social isolation were assessed in ARIC participants (visit 2: 1990-1992). Brain amyloid was evaluated with florbetapir PET standardized uptake value ratios (SUVRs; visit 5: 2012-2014)., Results: Among 316 participants without dementia, participants with intermediate (odds ratio (OR), 0.47; 95% CI, 0.25-0.88), or low social support (OR, 0.43; 95% CI, 0.22-0.83) in mid-life were less likely to have elevated amyloid SUVRs, relative to participants with high social support. Participants with moderate risk for social isolation in mid-life (OR, 0.32; 95% CI, 0.14-0.74) were less likely to have elevated amyloid burden than participants at low risk for social isolation. These associations were not significantly modified by sex or race., Conclusions: Lower social support and moderate risk of social isolation in mid-life were associated with lower odds of elevated amyloid SUVR in late life, compared to participants with greater mid-life psychosocial measures. Future longitudinal studies evaluating mid-life psychosocial factors, in relation to brain amyloid as well as other health outcomes, will strengthen our understanding of the role of these factors throughout the lifetime.

Study Objective: Identify optimal P2Y 12 inhibitor durations balancing ischemic-benefit and bleeding-risk outcomes after acute myocardial infarction (AMI) in older men and women., Design: Observational retrospective cohort with 2 years of follow-up, using clone-censor-weight marginal structural models to emulate randomization., Setting: 20 % sample of US Medicare administrative claims data., Participants: P2Y 12 inhibitor new users ≥66 years old following 2008-2013 AMI hospitalization., Exposures: 12- to 24-month P2Y 12 inhibitor durations in 1-month intervals., Main Outcome Measures: Effectiveness outcome (composite of all-cause mortality, recurrent AMI, ischemic stroke), safety outcome (hospitalized bleed), and negative control outcome (heart failure hospitalization)., Results: Of 28,488 P2Y 12 inhibitor new users, 51 % were female, 50 % were > 75 years old, 88 % were White/non-Hispanic, and 93 % initiated clopidogrel. Negative control outcome results for 16- through 24-month durations appeared most likely to meet assumptions of no unmeasured confounding. Compared to men taking 24-month therapy, men taking 16-month therapy had higher 2-year risks of the composite effectiveness outcome (relative risk [RR] = 1.08; 95 % confidence interval [95%CI]:1.00-1.15) with similar bleeding risks (RR = 0.98; 95%CI:0.85-1.13). Compared to women taking 24-month therapy, women taking 16-month therapy had similar 2-year risks of the composite effectiveness outcome (RR = 0.98; 95%CI:0.92-1.04) and lower bleeding risks (RR = 0.88; 95%CI:0.80-0.96)., Conclusions: Older men taking 24-month P2Y 12 inhibitor therapy had the lowest composite effectiveness outcome risk with no increased bleeding risk compared to shorter durations. Women taking 16-month versus 24-month P2Y 12 inhibitor therapy had similar composite effectiveness outcome risks but a substantially lower hospitalized bleeding risk, suggesting durations beyond 15-17 months lacked benefit while increasing bleeding risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Objectives: The COMPASS (COMprehensive Post-Acute Stroke Services) pragmatic trial cluster-randomized 40 hospitals in North Carolina to the COMPASS transitional care (TC) postacute care intervention or usual care. We estimated the difference in healthcare expenditures postdischarge for patients enrolled in the COMPASS-TC model of care compared with usual care., Methods: We linked data for patients with stroke or transient ischemic attack enrolled in the COMPASS trial with administrative claims from Medicare fee-for-service (n = 2262), Medicaid (n = 341), and a large private insurer (n = 234). The primary outcome was 90-day total expenditures, analyzed separately by payer. Secondary outcomes were total expenditures 30- and 365-days postdischarge and, among Medicare beneficiaries, expenditures by point of service. In addition to intent-to-treat analysis, we conducted a per-protocol analysis to compare Medicare patients who received the intervention with those who did not, using randomization status as an instrumental variable., Results: We found no statistically significant difference in total 90-day postacute expenditures between intervention and usual care; the results were consistent across payers. Medicare beneficiaries enrolled in the COMPASS intervention arm had higher 90-day hospital readmission expenditures ($682, 95% CI $60-$1305), 30-day emergency department expenditures ($132, 95% CI $13-$252), and 30-day ambulatory care expenditures ($67, 95% CI $38-$96) compared with usual care. The per-protocol analysis did not yield a significant difference in 90-day postacute care expenditures for Medicare COMPASS patients., Conclusions: The COMPASS-TC model did not significantly change patients' total healthcare expenditures for up to 1 year postdischarge., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Cognitive phenotyping is a widely used approach to characterize the heterogeneity of deficits in patients with a range of neurological disorders but has only recently been applied to patients with epilepsy. In this study, we identify cognitive phenotypes in older adults with late-onset epilepsy (LOE) and examine their demographic, clinical, and vascular profiles. Further, we examine whether specific phenotypes pose an increased risk for progressive cognitive decline., Methods: Participants were part of the Atherosclerosis Risk in Communities Study (ARIC), a prospective longitudinal community-based cohort study of 15,792 individuals initially enrolled in 1987-1989. LOE was identified from linked Centers for Medicare and Medicaid Services claims data. Ninety-one participants with LOE completed comprehensive testing either prior to or after seizure onset as part of a larger cohort in the ARIC Neurocognitive Study in either 2011-2013 or 2016-2017 (follow-up mean = 4.9 years). Cognitive phenotypes in individuals with LOE were derived by calculating test-level impairments for each participant (i.e., ≤1 SD below cognitively normal participants on measures of language, memory, and executive function/processing speed); and then assigning participants to phenotypes if they were impaired on at least two tests within a domain. The total number of impaired domains was used to determine the cognitive phenotypes (i.e., Minimal/No Impairment, Single Domain, or Multidomain)., Results: At our baseline (Visit 5), 36.3% met criteria for Minimal/No Impairment, 35% for Single Domain Impairment (with executive functioning/ processing speed impaired in 53.6%), and 28.7% for Multidomain Impairment. The Minimal/No Impairment group had higher education and occupational complexity. There were no differences in clinical or vascular risk factors across phenotypes. Of those participants with longitudinal data (Visit 6; n = 24), 62.5% declined (i.e., progressed to a more impaired phenotype) and 37.5% remained stable. Those who remained stable were more highly educated compared to those that declined., Discussion: Our results demonstrate the presence of identifiable cognitive phenotypes in older adults with LOE. These results also highlight the high prevalence of cognitive impairments across domains, with deficits in executive function/processing speed the most common isolated impairment. We also demonstrate that higher education was associated with a Minimal/No Impairment phenotype and lower risk for cognitive decline over time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Reyes, Schneider, Kucharska-Newton, Gottesman, Johnson and McDonald.)

Background: Multisystem dysregulation (Dm) shows promise as a metric of aging and predicts mortality. However, Dm needs to be studied with less severe endpoints indicating modifiable aging stages. Physical function, reflecting healthy longevity rather than just longevity, is more relevant to the goals of geroscience but has not been well investigated., Methods: We tested the association of midlife Dm and its change over ~20 years with physical function in later life in 5 583 the Atherosclerosis Risk in Communities Study cohort participants (baseline mean age 54.7). Dm quantifies the multivariate statistical deviation of 17 physiologically motivated biomarkers relative to their distribution in a young healthy sample at baseline. Physical function was assessed from grip strength and the Short Physical Performance Battery (SPPB). Associations were quantified using linear regression and ordinal logistic regression adjusting for age, sex, race, and education., Results: Each unit increment in midlife Dm was associated with 1.71 times the odds of having a lower SPPB score. Compared to the first quartile of midlife Dm, the odds ratios of having a lower SPPB score were 1.25, 1.56, and 2.45, respectively, for the second-fourth quartiles. Similar graded association patterns were observed for each SPPB component test and grip strength. An inverse monotonic relationship also was observed between the annual growth rate of Dm and physical function., Conclusion: Greater Dm and progression in midlife were associated with lower physical function in later life. Future studies on the factors that lead to the progression of Dm may highlight opportunities to preserve physical function., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Early-life socioeconomic adversity may be associated with poor cognitive health over the life course., Objective: To examine the association of childhood and midlife neighborhood socioeconomic position (nSEP) with cognitive decline., Design, Setting, and Participants: This cohort study included 5711 men and women enrolled in the community-based Atherosclerosis Risk in Communities (ARIC) Study with repeated cognitive data measured over a median 27.0 years (IQR, 26.0-27.9 years) (1990-2019). Statistical analysis was performed from December 2022 through March 2023., Exposure: Residence addresses for ARIC Study cohort participants were obtained at midlife (1990-1993) and as recalled addresses at 10 years of age (childhood). A composite nSEP z score was created as a sum of z scores for US Census-based measures of median household income; median value of owner-occupied housing units; percentage of households receiving interest, dividend, or net rental income; percentage of adults with a high school degree; percentage of adults with a college degree; and percentage of adults in professional, managerial, or executive occupations. Childhood nSEP and midlife nSEP were modeled as continuous measures and discretized into tertiles., Main Outcomes and Measures: A factor score for global cognition was derived from a battery of cognitive tests administered at 5 in-person visits from baseline to 2019. The rate of cognitive decline from 50 to 90 years of age was calculated by fitting mixed-effects linear regression models with age as the time scale and adjusted for race, sex, birth decade, educational level, and presence of the apolipoprotein E ε4 allele., Results: Among 5711 ARIC Study participants (mean [SD] baseline age, 55.1 [4.7] years; 3372 women [59.0%]; and 1313 Black participants [23.0%]), the median rate of cognitive decline was -0.33 SDs (IQR, -0.49 to -0.20 SDs) per decade. In adjusted analyses, each 1-SD-higher childhood nSEP score was associated with a slower (β, -9.2%; 95% CI, -12.1% to -6.4%) rate of cognitive decline relative to the sample median. A comparable association was observed when comparing the highest tertile with the lowest tertile of childhood nSEP (β, -17.7%; 95% CI, -24.1% to -11.3%). Midlife nSEP was not associated with the rate of cognitive decline., Conclusions and Relevance: In this cohort study of contextual factors associated with cognitive decline, childhood nSEP was inversely associated with trajectories of cognitive function throughout adulthood.

Background: Stroke patients discharged home often require prolonged assistance from caregivers. Little is known about the real-world effectiveness of a comprehensive stroke transitional care intervention on relieving caregiver strain., Objectives: To describe the effect of the COMPASS transitional care (COMPASS-TC) intervention on caregiver strain and characterize the types, duration, and intensity of caregiving., Methods: The cluster-randomized COMPASS pragmatic trial evaluated the effectiveness of COMPASS-TC versus usual care with patients with mild stroke and TIA at 40 hospitals in North Carolina, USA. Of 5882 patients enrolled, 4208 (71%) identified a familial caregiver. A follow-up Caregiver Questionnaire, including the Modified Caregiver Strain Index, was administered at approximately three months post-discharge. Demographics and frequency, duration, and intensity of caregiving were compared between groups., Results: 1228 caregivers (29%) completed the questionnaire. Completion was positively associated with older patient age, white race, and spousal relationship. One-third of the caregivers provided ≥30 hours of care per week and 889 (79%) provided care ≥9 weeks. Average standardized caregiver strain was 21.9 (0-100), increasing with stroke severity and comorbidity burden. Women caregivers reported higher strain than men. Treatment allocation was not associated with caregiver strain., Conclusions: This sample of mild stroke and TIA survivors received significant assistance from familial caregivers. However, caregiver strain was relatively low. Findings support the importance of familial caregiving in stroke, the continued disproportionate burden on women within the family, and the need for future research on caregiver support.

Background: Early-onset hypertensive disorders of pregnancy (eHDP) are associated with more severe maternal and infant outcomes than later-onset disease. However, little has been done to evaluate population-level trends. Therefore, in this paper, we seek to address this understudied area by describing the geospatial and temporal patterns of county-level incidence of eHDP and assessing county-level demographics that may be associated with an increased incidence of eHDP., Methods: Employing Kentucky certificates of live and stillbirth from 2008-2017, this ecological study detected county-level clusters of early-onset hypertensive disorders of pregnancy using SaTScan, calculated average annual percent change (AAPC) with a join point analysis, and identified county-level covariates (% of births to women ≥ 35 years of age, % with BMI ≥ 30 kg/m 2 , % currently smoking, % married, and % experienced eHDP) with a fixed-effects negative binomial regression model for longitudinal data with an autoregressive (AR) correlation structure offset with the natural log of the number of births in each county and year., Results: County-level incidence of eHDP had a non-statistically significant increase of almost 3% (AAPC: 2.84, 95% CI: -4.26, 10.46), while maternal smoking decreased by almost 6% over the study period (AAPC:-5.8%, 95%CI: -7.5, -4.1), Risk factors for eHDP such as pre-pregnancy BMI ≥ 30 and proportion of births to women ≥ 35 years of age increased by 2.3% and 3.4% respectively (BMI AAPC:2.3, 95% CI: 0.94, 3.7; ≥ 35 years AAPC:3.4, 95% CI: 0.66, 6.3). After adjusting for race, county-level proportions of college attainment, and maternal smoking throughout pregnancy, counties with the highest proportion of births to women with BMI ≥ 30 kg/m 2 reported an eHDP incidence 20% higher than counties with a lower proportion of births to mothers with a BMI ≥ 30 kg/m 2 and a 20% increase in eHDP incidence (aRR = 1.20, 95% CI: 1.00, 1.44). We also observed that counties with the highest proportion vs. the lowest of mothers ≥ 35 years old (> 6.1%) had a 26% higher incidence of eHDP (RR = 1.26, 95%CI: 1.04, 1.50) compared to counties with the lowest incidence (< 2.5%). We further identified two county-level clusters of elevated eHDP rates. We also observed that counties with the highest vs. lowest proportion of mothers ≥ 34 years old (> 6.1% vs. < 2.5%) had a 26% increase in the incidence of eHDP (RR = 1.26, 95% CI: 1.04, 1.50). We further identified two county-level clusters of elevated incidence of eHDP., Conclusions: This study identified two county-level clusters of eHDP, county-level covariates associated with eHDP, and that while increasing, the average rate of increase for eHDP was not statistically significant. This study also identified the reduction in maternal smoking over the study period and the concerning increase in rates of elevated pre-pregnancy BMI among mothers. Further work to explore the population-level trends in this understudied pregnancy complication is needed to identify community factors that may contribute to disease and inform prevention strategies., (© 2023. The Author(s).)

Background and Objectives: We examined transitional care management within 90 days and 1 year following discharge home among acute stroke and transient ischemic attack patients from the Comprehensive Post-Acute Stroke Services (COMPASS) Study, a cluster-randomized pragmatic trial of early supported discharge conducted in 41 hospitals (40 hospital units) in North Carolina, United States., Methods: Data for 2262 of the total 6024 (37.6%; 1069 intervention and 1193 usual care) COMPASS patients were linked with the Centers for Medicare and Medicaid Services fee-for-service Medicare claims. Time to the first ambulatory care visit was examined using Cox proportional hazard models adjusted for patient characteristics not included in the randomization protocol., Results: Only 6% of the patients [mean (SD) age 74.9 (10.2) years, 52.1% women, 80.3% White)] did not have an ambulatory care visit within 90 days postdischarge. Mean time (SD) to first ambulatory care visit was 12.0 (26.0) and 16.3 (35.1) days in intervention and usual care arms, respectively, with the majority of visits in both study arms to primary care providers. The COMPASS intervention resulted in a 27% greater use of ambulatory care services within 1 year postdischarge, relative to usual care [HR=1.27 (95% CI: 1.14-1.41)]. The use of transitional care billing codes was significantly greater in the intervention arm as compared with usual care [OR=1.87 (95% CI: 1.54-2.27)]., Discussion: The COMPASS intervention, which was aimed at improving stroke post-acute care, was associated with an increase in the use of ambulatory care services by stroke and transient ischemic attack patients discharged home and an increased use of transitional care billing codes by ambulatory providers., Competing Interests: P.W.D. and C.D.B. report ownership interest in Care Directions, Inc.; Duncan is a research advisor for BQ Technologies. The remaining authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: As opioid prescriptions have risen, there has also been an increase in opioid use disorder (OUD) and its adverse outcomes. Accurate and complete epidemiologic surveillance of OUD, to inform prevention strategies, presents challenges. The objective of this study was to ascertain prevalence of OUD using two methods to identify OUD in electronic health records (EHR): applying natural language processing (NLP) for text mining of unstructured clinical notes and using ICD-10-CM diagnostic codes., Methods: Data were drawn from EHR records for hospital and emergency department patient visits to a large regional academic medical center from 2017 to 2019. International Classification of Disease, 10th Edition, Clinic Modification (ICD-10-CM) discharge codes were extracted for each visit. To develop the rule-based NLP algorithm, a stepwise process was used. First, a small sample of visits from 2017 was used to develop initial dictionaries. Next, EHR corresponding to 30,124 visits from 2018 were used to develop and evaluate the rule-based algorithm. A random sample of the results were manually reviewed to identify and address shortcomings in the algorithm, and to estimate sensitivity and specificity of the two methods of ascertainment. Last, the final algorithm was then applied to 29,212 visits from 2019 to estimate OUD prevalence., Results: While there was substantial overlap in the identified records (n = 1,381 [59.2 %]), overall n = 2,332 unique visits were identified. Of the total unique visits, 430 (18.4 %) were identified only by ICD-10-CM codes, and 521 (22.3 %) were identified only by NLP. The prevalence of visits with evidence of an OUD diagnosis in this sample, ascertained using only ICD-10-CM codes, was 1,811/29,212 (6.1 %). Including the additional 521 visits identified only by NLP, the estimated prevalence of OUD is 2,332/29,212 (7.9 %), an increase of 29.5 % compared to the use of ICD-10-CM codes alone. The estimated sensitivity and specificity of the NLP-based OUD classification were 81.8 % and 97.5 %, respectively, relative to gold-standard manual review by an expert addiction medicine physician., Conclusion: NLP-based algorithms can automate data extraction and identify evidence of opioid use disorder from unstructured electronic healthcare records. The most complete ascertainment of OUD in EHR was combined NLP with ICD-10-CM codes. NLP should be considered for epidemiological studies involving EHR data., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: Our objective was to describe characteristics of patients presenting with and without ischemic pain among those diagnosed with acute myocardial infarction (MI) using individual-level data from the Atherosclerosis Risk in Communities Study from 2005 to 2019., Methods: Acute MI included events deemed definite or probable MI by a physician panel based on ischemic pain, cardiac biomarkers, and ECG evidence. Patient characteristics included age at hospitalization, sex, race/ethnicity, comorbidities (smoking status, diabetes, hypertension, history of previous stroke, MI, or cardiovascular procedure, and history of valvular disease or cardiomyopathy) and in-hospital complications occurring during the event of interest (pulmonary edema, pulmonary embolism, in-hospital stroke, pneumonia, cardiogenic shock, ventricular fibrillation). Analyses were stratified by MI subtype (STEMI, NSTEMI, Unclassified) and patient characteristics and 28-day case fatality was compared between MI presenting with or without ischemic pain., Results: Between 2005 and 2019, there were 1711 hospitalized definite/probable MI events (47 % female, 26 % black, and age of 78 [6.7 years]). A smaller proportion of STEMI patients presented without ischemic pain compared to NSTEMI patients (20 % vs 32 %). Race, sex, age, and comorbidity profiles did not differ significantly across ischemic pain presentations. Patients presenting without ischemic pain had a higher 28-day all-cause case fatality after adjusting for age, race, sex, and comorbidities. However, after further adjustment, time from symptom onset to hospital arrival, time to treatment, and in-hospital complications explained the difference in 28-day case fatality between ischemic pain presentations., Conclusions: Future research should focus on differences in treatment delay across ischemic pain presentations rather than sex differences in acute coronary syndrome presentation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

We investigated the association of lung function at mid-life, later in life, and its 20-year decline, with arterial stiffness later in life. We examined 5720 Atherosclerosis Risk in Communities Study participants who attended Visits 1 (1987-1989) and 5 (2011-2013). Lung function measures were forced expiratory volume in one second (FEV 1 ) and forced vital capacity (FVC), obtained at Visits 1, 2 (1990-1992), and 5. Central artery stiffness (carotid-femoral pulse wave velocity [cfPWV]) was measured at Visit 5. We evaluated associations of lung function with later-life central artery stiffness and cfPWV >75th percentile by multivariable linear and logistic regressions. Lung function at Visit 1 (FEV 1 β: -26, 95% Confidence Interval [CI]: -48, -5; FVC β: -14, 95% CI: -32, 5) and Visit 5 (FEV 1 β: -22, 95% CI: -46, 2; FVC β: -18, 95% CI: -38, 2) were inversely associated with cfPWV at Visit 5, and with odds of high cfPWV in fully adjusted models. Twenty-year decline in lung function was not associated with continuous or dichotomous measures of arterial stiffness (FEV 1 β: 11, 95% CI: -46, 68; FVC β: -4, 95% CI: -52, 43). Lung function at mid-life and late-life was inversely associated with arterial stiffness in later life.

Background: Although a few studies reported an association between varicose veins and physical function, this potentially bidirectional association has not been systematically evaluated in the general population., Method: In 5 580 participants (aged 71-90 years) from the Atherosclerosis Risk in Communities study, varicose veins were identified in outpatient and inpatient administrative data prior to (prevalent cases) and after (incident cases) visit 5 (2011-2013). Physical function was evaluated by the Short Physical Performance Battery (SPPB, score ranging from 0 to 12). We evaluated (i) cross-sectional association between prevalent varicose veins and physical function, (ii) association of prevalent varicose veins with subsequent changes in physical function from visit 5 to visits 6 (2016-2017) and 7 (2018-2019), and (iii) association of physical function at visit 5 with incident varicose veins during a median follow-up of 3.6 years (105 incident varicose veins among 5 350 participants without prevalent cases at baseline)., Results: At baseline, varicose veins were recognized in 230 (4.1%) participants and cross-sectionally associated with reduced physical function. Longitudinally, prevalent varicose veins were not significantly associated with a decline in SPPB over time. In contrast, a low SPPB ≤6 was associated with a greater incidence of varicose veins compared to SPPB ≥10 (adjusted hazard ratio 2.13 [95% confidence interval = 1.19, 3.81])., Conclusion: In community-dwelling older adults, varicose veins and low physical function were associated cross-sectionally. Longitudinally, low physical function was a risk factor for incident varicose veins, but not vice versa. Our findings suggest an etiological contribution of low physical function to incident varicose veins., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To examine the effect of a comprehensive transitional care model on the use of skilled nursing facility (SNF) and inpatient rehabilitation facility (IRF) care in the 12 months after acute care discharge home following stroke; and to identify predictors of experiencing a SNF or IRF admission following discharge home after stroke., Design: Cluster randomized pragmatic trial SETTING: Forty-one acute care hospitals in North Carolina., Participants: 2262 Medicare fee-for-service beneficiaries with transient ischemic attack or stroke discharged home. The sample was 80.3% White and 52.1% female, with a mean (SD) age of 74.9 (10.2) years and a mean ± SD National Institutes of Health stroke scale score of 2.3 (3.7)., Intervention: Comprehensive transitional care model (COMPASS-TC), which consisted of a 2-day follow-up phone call from the postacute care coordinator and 14-day in-person visit with the postacute care coordinator and advanced practice provider., Main Outcome Measures: Time to first SNF or IRF and SNF or IRF admission (yes/no) in the 12 months following discharge home. All analyses utilized multivariable mixed models including a hospital-specific random effect to account for the non-independence of measures within hospital. Intent to treat analyses using Cox proportional hazards regression assessed the effect of COMPASS-TC on time to SNF/IRF admission. Logistic regression was used to identify clinical and non-clinical predictors of SNF/IRF admission., Results: Only 34% of patients in the intervention arm received COMPASS-TC per protocol. COMPASS-TC was not associated with a reduced hazard of a SNF/ IRF admission in the 12 months post-discharge (hazard ratio, 1.20, with a range of 0.95-1.52) compared to usual care. This estimate was robust to additional covariate adjustment (hazard ratio, 1.23) (0.93-1.64). Both clinical and non-clinical factors (ie, insurance, geography) were predictors of SNF/IRF use., Conclusions: COMPASS-TC was not consistently incorporated into real-world clinical practice. The use of a comprehensive transitional care model for patients discharged home after stroke was not associated with SNF or IRF admissions in a 12-month follow-up period. Non-clinical factors predictive of SNF/IRF use suggest potential issues with access to this type of care., (Copyright © 2021 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Falls are a major public health problem affecting millions of older adults each year. Little is known about FRID prescribing behaviors after injurious falls occur. The primary objective of this study was to investigate whether an injurious fall is associated with being prescribed a new FRID., Methods: We conducted a cross-sectional analysis using data from the National Ambulatory Medical Care Survey (2016). We included visits from patients age ≥ 65 years and classified visits based on presence of an injurious fall. The outcome of interest was prescription of new FRID between those with and without an injurious fall. Multivariable logistic regression weighted for sampling and adjusted for demographics, health history and other medications was used. Age and Alzheimer's disease were examined as potential effect measure modifiers. Odds ratios and 95% confidence intervals were reported. Bayes factor upper bounds were also reported to quantify whether the data were better predicted by the null hypothesis or the alternative hypothesis., Results: The sample included 239,016,482 ambulatory care visits. 5,095,734 (2.1%) of the visits were related to an injurious fall. An injurious fall was associated with a non-statistically significant increase in odds of at least one new FRID prescription: adjusted OR = 1.6 (95% CI 0.6, 4.0). However, there was non-statistically significant evidence that the association depended on patient age, with OR = 2.6 (95% CI 0.9, 7.4) for ages 65-74 versus OR = 0.4 (95% CI 0.1, 1.6) for ages ≥ 75. In addition to age, Alzheimer's disease was also identified as a statistically significant effect measure modifier, but stratum specific estimates were not determined due to small sample sizes., Conclusions: Ambulatory care visits involving an injurious fall showed a non-statistically significant increase in odds of generating a new FRID prescription, but this association may depend on age., (© 2022. The Author(s).)

Objective: Electronic health record (EHR) data are underutilized for abstracting classification criteria for heart disease. We compared extraction of EHR data on troponin I and T levels with human abstraction., Methods: Using EHR for hospitalizations identified through the Atherosclerosis Risk in Communities (ARIC) Study in four US hospitals, we compared blood levels of troponins I and T extracted from EHR structured data elements with levels obtained through data abstraction by human abstractors to 3 decimal places. Observations were divided randomly 50/50 into training and validation sets. Bayesian multilevel logistic regression models were used to estimate agreement by hospital in first and maximum troponin levels, troponin assessment date, troponin upper limit of normal (ULN), and classification of troponin levels as normal (< ULN), equivocal (1-2× ULN), abnormal (>2× ULN), or missing., Results: Estimated overall agreement in first measured troponin level in the validation data was 88.2% (95% credible interval: 65.0%-97.5%) and 95.5% (91.2-98.2%) for the maximum troponin level observed during hospitalization. The largest variation in probability of agreement was for first troponin measured, which ranged from 66.4% to 95.8% among hospitals., Conclusion: Extraction of maximum troponin values during a hospitalization from EHR structured data is feasible and accurate., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background Mortality and hospital readmission rates may reflect the quality of acute and postacute stroke care. Our aim was to investigate if, compared with usual care (UC), the COMPASS-TC (Comprehensive Post-Acute Stroke Services Transitional Care) intervention (INV) resulted in lower all-cause and stroke-specific readmissions and mortality among patients with minor stroke and transient ischemic attack discharged from 40 diverse North Carolina hospitals from 2016 to 2018. Methods and Results Using Medicare fee-for-service claims linked with COMPASS cluster-randomized trial data, we performed intention-to-treat analyses for 30-day, 90-day, and 1-year unplanned all-cause and stroke-specific readmissions and all-cause mortality between INV and UC groups, with 90-day unplanned all-cause readmissions as the primary outcome. Effect estimates were determined via mixed logistic or Cox proportional hazards regression models adjusted for age, sex, race, stroke severity, stroke diagnosis, and documented history of stroke. The final analysis cohort included 1069 INV and 1193 UC patients (median age 74 years, 80% White, 52% women, 40% with transient ischemic attack) with median length of hospital stay of 2 days. The risk of unplanned all-cause readmission was similar between INV versus UC at 30 (9.9% versus 8.7%) and 90 days (19.9% versus 18.9%), respectively. No significant differences between randomization groups were seen in 1-year all-cause readmissions, stroke-specific readmissions, or mortality. Conclusions In this pragmatic trial of patients with complex minor stroke/transient ischemic attack, there was no difference in the risk of readmission or mortality with COMPASS-TC relative to UC. Our study could not conclusively determine the reason for the lack of effectiveness of the INV. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02588664.

Objectives: To determine if comparable older women and men received different durations of P2Y 12 inhibitor therapy following acute myocardial infarction (AMI) and if therapy duration differences were justified by differences in ischaemic benefits and/or bleeding risks., Design: Retrospective cohort., Setting: 20% sample of 2007-2015 US Medicare fee-for-service administrative claims data., Participants: ≥66-year-old P2Y 12 inhibitor new users following 2008-2013 AMI hospitalisation (N=30 613). Older women compared to older men with similar predicted risks of study outcomes., Primary and Secondary Outcome Measures: Primary outcome: P2Y 12 inhibitor duration (modelled as risk of therapy discontinuation)., Secondary Outcomes: clinical events while on P2Y 12 inhibitor therapy, including (1) death/hospice admission, (2) composite of ischaemic events (AMI/stroke/revascularisation) and (3) hospitalised bleeds. Cause-specific risks and relative risks (RRs) estimated using Aalen-Johansen cumulative incidence curves and bootstrapped 95% CIs., Results: 10 486 women matched to 10 486 men with comparable predicted risks of all 4 study outcomes. No difference in treatment discontinuation was observed at 12 months (women 31.2% risk; men 30.9% risk; RR 1.01; 95% CI 0.97 to 1.05), but women were more likely than men to discontinue therapy at 24 months (54.4% and 52.9% risk, respectively; RR 1.03; 95% CI 1.00 to 1.05). Among patients who did not discontinue P2Y 12 inhibitor therapy, women had lower 24-month risks of ischaemic outcomes than men (13.1% and 14.7%, respectively; RR 0.90; 95% CI 0.84 to 0.96), potentially lower 24-month risks of death/hospice admission (5.0% and 5.5%, respectively; RR 0.91; 95% CI 0.82 to 1.02), but women and men both had 2.5% 24-month bleeding risks (RR 0.98; 95% CI 0.82 to 1.14)., Conclusions: Risks for death/hospice and ischaemic events were lower among women still taking a P2Y 12 inhibitor than comparable men, with no difference in bleeding risks. Shorter P2Y 12 inhibitor durations in older women than comparable men observed between 12 and 24 months post-AMI may reflect a disparity that is not justified by differences in clinical need., Competing Interests: Competing interests: None declared., (© 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.)

Bundled payments are a promising alternative payment model for reducing costs and improving the coordination of postacute stroke care, yet there is limited evidence supporting the effectiveness of bundled payments for stroke. This may be due to the lack of effective strategies to address the complex needs of stroke survivors. In this article, we describe COMprehensive Post-Acute Stroke Services (COMPASS), a comprehensive transitional care intervention focused on discharge from the acute care setting to home. COMPASS may serve as a potential care redesign strategy under bundled payments for stroke, such as the Centers for Medicare & Medicaid Innovation Bundled Payment for Care Improvement Initiative. The COMPASS care model is aligned with the incentive structures and essential components of bundled payments in terms of care coordination, patient assessment, patient and family involvement, and continuity of care. Ongoing evaluation will inform the design of incorporating COMPASS-like transitional care interventions into a stroke bundle., (Copyright © 2021 The American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

BACKGROUND In this scoping review, we identified and reviewed 23 original articles from the PubMed database that investigated the relationship between nonacute opioid use (NOU) and cardiovascular outcomes. METHODS AND RESULTS We defined NOU to include both long-term opioid therapy and opioid use disorder. We summarized the association between NOU and 5 classes of cardiovascular disease, including infective endocarditis, coronary heart disease (including myocardial infarction), congestive heart failure, cardiac arrythmia (including cardiac arrest), and stroke. The most commonly studied outcomes were coronary heart disease and infective endocarditis. There was generally consistent evidence of a positive association between community prevalence of injection drug use (with opioids being the most commonly injected type of drug) and community prevalence of infective endocarditis, and between (primarily medically indicated) NOU and myocardial infarction. There was less consensus about the relationship between NOU and congestive heart failure, cardiac arrhythmia, and stroke. CONCLUSIONS There is a dearth of high-quality evidence on the relationship between NOU and cardiovascular disease. Innovative approaches to the assessment of opioid exposure over extended periods of time will be required to address this need.

Background: Whether high burden of subclinical vascular disease (SVD) is associated with increased premature mortality among middle-aged adults is not adequately understood. The association of midlife SVD burden with premature mortality among middle-aged adults free of clinical cardiovascular disease (CVD) could provide further insights into stratifying premature death beyond clinical CVD., Objective: To determine whether high burden of subclinical vascular disease is associated with increased premature mortality among middle-aged adults., Design: We leveraged data from the Atherosclerosis Risk in Communities Study., Participants: Thirteen thousand eight hundred seventy-six community-dwelling blacks and whites aged 45-64 years from the Atherosclerosis Risk in Communities Study., Main Measures: Each SVD measure-ankle-brachial index, carotid intima-media thickness, and electrocardiogram-was scored 0 (no abnormalities), 1 (minor abnormalities), or 2 (major abnormalities). An index was constructed as the sum of three measures, ranging from 0 (lowest burden) to 6 (highest burden). We used the Cox proportional-hazards model to determine the association of SVD burden with premature mortality (death before age 70) among persons free of clinical CVD. We then tested the difference in point estimates between SVD and clinical CVD., Key Results: Among persons without CVD, the premature death was 1.7, 2.1, 2.5, and 3.8 per 1000 person-years among those with an SVD score of 0 (lowest burden), 1, 2, and 3-6 (highest burden), respectively. After multivariable-adjustment, highest SVD burden (score = 3-6; HR = 1.47) was significantly associated with premature death among persons initially without CVD. In the model where persons with and without CVD were included, high SVD burden (score: 3-6 vs. 0) and CVD did not have hugely different association with premature death (HR = 1.49 vs. 1.68; P = 0.32 for comparison)., Conclusions: Midlife SVD burden was associated with premature mortality and it could stratify premature death beyond clinical CVD. It is important to take SVD into account when designing interventions for reducing premature mortality., (© 2021. Society of General Internal Medicine.)

Objectives: Using free-text clinical notes and reports from hospitalised patients, determine the performance of natural language processing (NLP) ascertainment of Framingham heart failure (HF) criteria and phenotype., Study Design: A retrospective observational study design of patients hospitalised in 2015 from four hospitals participating in the Atherosclerosis Risk in Communities (ARIC) study was used to determine NLP performance in the ascertainment of Framingham HF criteria and phenotype., Setting: Four ARIC study hospitals, each representing an ARIC study region in the USA., Participants: A stratified random sample of hospitalisations identified using a broad range of International Classification of Disease, ninth revision, diagnostic codes indicative of an HF event and occurring during 2015 was drawn for this study. A randomly selected set of 394 hospitalisations was used as the derivation dataset and 406 hospitalisations was used as the validation dataset., Intervention: Use of NLP on free-text clinical notes and reports to ascertain Framingham HF criteria and phenotype., Primary and Secondary Outcome Measures: NLP performance as measured by sensitivity, specificity, positive-predictive value (PPV) and agreement in ascertainment of Framingham HF criteria and phenotype. Manual medical record review by trained ARIC abstractors was used as the reference standard., Results: Overall, performance of NLP ascertainment of Framingham HF phenotype in the validation dataset was good, with 78.8%, 81.7%, 84.4% and 80.0% for sensitivity, specificity, PPV and agreement, respectively., Conclusions: By decreasing the need for manual chart review, our results on the use of NLP to ascertain Framingham HF phenotype from free-text electronic health record data suggest that validated NLP technology holds the potential for significantly improving the feasibility and efficiency of conducting large-scale epidemiologic surveillance of HF prevalence and incidence., Competing Interests: Competing interests: None declared., (© 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: The COMprehensive Post-Acute Stroke Services (COMPASS) model, a transitional care intervention for stroke patients discharged home, was tested against status quo postacute stroke care in a cluster-randomized trial in 40 hospitals in North Carolina. This study examined the hospital-level costs associated with implementing and sustaining COMPASS., Methods: Using an activity-based costing survey, we estimated hospital-level resource costs spent on COMPASS-related activities during approximately 1 year. We identified hospitals that were actively engaged in COMPASS during the year before the survey and collected resource cost estimates from 22 hospitals. We used median wage data from the Bureau of Labor Statistics and COMPASS enrollment data to estimate the hospital-level costs per COMPASS enrollee., Results: Between November 2017 and March 2019, 1582 patients received the COMPASS intervention across the 22 hospitals included in this analysis. Average annual hospital-level COMPASS costs were $2861 per patient (25th percentile: $735; 75th percentile: $3,475). Having 10% higher stroke patient volume was associated with 5.1% lower COMPASS costs per patient (P=0.016). About half (N=10) of hospitals reported postacute clinic visits as their highest-cost activity, while a third (N=7) reported case ascertainment (ie, identifying eligible patients) as their highest-cost activity., Conclusions: We found that the costs of implementing COMPASS varied across hospitals. On average, hospitals with higher stroke volume and higher enrollment reported lower costs per patient. Based on average costs of COMPASS and readmissions for stroke patients, COMPASS could lower net costs if the model is able to prevent about 6 readmissions per year., Competing Interests: P.W.D. and C.D.B.: Ownership in Care Directions LLC. The remaining authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine the association between dietary intake of choline and betaine and the risk of type 2 diabetes., Research Design and Methods: Among 13,440 Atherosclerosis Risk in Communities (ARIC) study participants, the prospective longitudinal association between dietary choline and betaine intake and the risk of type 2 diabetes was assessed using interval-censored Cox proportional hazards and logistic regression models adjusted for baseline potential confounding variables., Results: Among 13,440 participants (55% women, mean age 54 [SD 7.4] years), 1,396 developed incident type 2 diabetes during median follow-up of 9 years from 1987 to 1998. There was no statistically significant association between every 1-SD increase in dietary choline and risk of type 2 diabetes (hazard ratio [HR] 1.01 [95% CI 0.87, 1.16]) nor between dietary betaine intake and the risk of type 2 diabetes (HR 1.01 [0.94, 1.10]). Those in the highest quartile of dietary choline intake did not have a statistically significant higher risk of type 2 diabetes than those in the lowest choline quartile (HR 1.09 [0.84, 1.42]); similarly, dietary betaine intake was not associated with the risk of type 2 diabetes comparing the highest quartile to the lowest (HR 1.06 [0.87, 1.29]). Among women, there was a higher risk of type 2 diabetes, comparing the highest to lowest dietary choline quartile (HR 1.54 [1.06, 2.25]), while in men, the association was null (HR 0.82 [0.57, 1.17]). Nevertheless, there was a nonsignificant interaction between high choline intake and sex on the risk of type 2 diabetes ( P = 0.07). The results from logistic regression were similar., Conclusions: Overall and among male participants, dietary choline or betaine intakes were not associated with the risk of type 2 diabetes. Among female participants, there was a trend for a modestly higher risk of type 2 diabetes among those with the highest as compared with the lowest quartile of dietary choline intake. Our study should inform clinical trials on dietary choline and betaine supplementation in relationship with the risk of type 2 diabetes., (© 2020 by the American Diabetes Association.)

Background The objectives of this study were to develop and test in real-world clinical practice the effectiveness of a comprehensive postacute stroke transitional care (TC) management program. Methods and Results The COMPASS study (Comprehensive Post-Acute Stroke Services) was a pragmatic cluster-randomized trial where the hospital was the unit of randomization. The intervention (COMPASS-TC) was initiated at 20 hospitals, and 20 hospitals provided their usual care. Hospital staff enrolled 6024 adult stroke and transient ischemic attack patients discharged home between 2016 and 2018. COMPASS-TC was patient-centered and assessed social and functional determinates of health to inform individualized care plans. Ninety-day outcomes were evaluated by blinded telephone interviewers. The primary outcome was functional status (Stroke Impact Scale-16); secondary outcomes were mortality, disability, medication adherence, depression, cognition, self-rated health, fatigue, care satisfaction, home blood pressure monitoring, and falls. The primary analysis was intention to treat. Of intervention hospitals, 58% had uninterrupted intervention delivery. Thirty-five percent of patients at intervention hospitals attended a COMPASS clinic visit. The primary outcome was measured for 59% of patients and was not significantly influenced by the intervention. Mean Stroke Impact Scale-16 (±SD) was 80.6±21.1 in TC versus 79.9±21.4 in usual care. Home blood pressure monitoring was self-reported by 72% of intervention patients versus 64% of usual care patients (adjusted odds ratio, 1.43 [95% CI, 1.21-1.70]). No other secondary outcomes differed. Conclusions Although designed according to the best available evidence with input from various stakeholders and consistent with Centers for Medicare and Medicaid Services TC policies, the COMPASS model of TC was not consistently incorporated into real-world health care. We found no significant effect of the intervention on functional status at 90 days post-discharge. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02588664.

Background: The COMprehensive Post-Acute Stroke Services (COMPASS) pragmatic trial compared the effectiveness of comprehensive transitional care (COMPASS-TC) versus usual care among stroke and transient ischemic attack (TIA) patients discharged home from North Carolina hospitals. We evaluated implementation of COMPASS-TC in 20 hospitals randomized to the intervention using the RE-AIM framework., Methods: We evaluated hospital-level Adoption of COMPASS-TC; patient Reach (meeting transitional care management requirements of timely telephone and face-to-face follow-up); Implementation using hospital quality measures (concurrent enrollment, two-day telephone follow-up, 14-day clinic visit scheduling); and hospital-level sustainability (Maintenance). Effectiveness compared 90-day physical function (Stroke Impact Scale-16), between patients receiving COMPASS-TC versus not. Associations between hospital and patient characteristics with Implementation and Reach measures were estimated with mixed logistic regression models., Results: Adoption: Of 95 eligible hospitals, 41 (43%) participated in the trial. Of the 20 hospitals randomized to the intervention, 19 (95%) initiated COMPASS-TC. Reach: A total of 24% (656/2751) of patients enrolled received a billable TC intervention, ranging from 6 to 66% across hospitals., Implementation: Of eligible patients enrolled, 75.9% received two-day calls (or two attempts) and 77.5% were scheduled/offered clinic visits. Most completed visits (78% of 975) occurred within 14 days. Effectiveness: Physical function was better among patients who attended a 14-day visit versus those who did not (adjusted mean difference: 3.84, 95% CI 1.42-6.27, p = 0.002). Maintenance: Of the 19 adopting hospitals, 14 (74%) sustained COMPASS-TC., Conclusions: COMPASS-TC implementation varied widely. The greatest challenge was reaching patients because of system difficulties maintaining consistent delivery of follow-up visits and patient preferences to pursue alternate post-acute care. Receiving COMPASS-TC was associated with better functional status., Trial Registration: ClinicalTrials.gov number: NCT02588664. Registered 28 October 2015.

Objective: To identify the association between brain vascular changes and cortical volumes on MRI and late-onset epilepsy., Methods: In 1993-1995, 1,920 participants (median age 62.7, 59.9% female) in the community-based Atherosclerosis Risk in Communities (ARIC) Study underwent MRI, and white matter hyperintensities were measured. In addition, in 2011-2013, 1,964 ARIC participants (median age 72.4, 61.1% female) underwent MRI, and cortical volumes and white matter hyperintensities were measured. We identified cases of late-onset epilepsy (starting at age 60 or later) from ARIC hospitalization records and Medicare claims data. Using the 1993-1995 MRI, we evaluated the association between white matter hyperintensities and subsequent epilepsy using survival analysis. We used the 2011-2013 MRI to conduct cross-sectional logistic regression to examine the association of cortical volumes and white matter hyperintensities with late-onset epilepsy. All models were adjusted for demographics, hypertension, diabetes, smoking, and APOE ε4 allele status., Results: Ninety-seven ARIC participants developed epilepsy after having an MRI in 1993-1995 (incidence 3.34 per 1,000 person-years). The degree of white matter hyperintensities measured at ages 49-72 years was associated with the risk of late-onset epilepsy (hazard ratio 1.27 per age-adjusted SD, 95% confidence interval [CI] 1.06-1.54). Lower cortical volume scores were associated cross-sectionally with higher odds of late-onset epilepsy (odds ratio 1.87, 95% CI 1.16-3.02) per age-adjusted SD., Conclusions: This study demonstrates associations between earlier-life white matter hyperintensities on MRI and later-life incident epilepsy, and between cortical volumes measured later in life and late-onset epilepsy. These findings may help illuminate the causes of late-onset epilepsy., (© 2019 American Academy of Neurology.)

Objective: This study (1) describes transitional care for stroke patients discharged home from hospitals, (2) compares hospitals' standards of transitional care with core transitional care management (TCM) components recognized by Medicare, and (3) examines the association of policy and hospital specialty designations with TCM implementation., Methods: Hospitals participating in the Comprehensive Post-Acute Stroke Services (COMPASS) Study provided data on their hospital, stroke patient population, and standards of transitional care. Hospital-reported transitional care strategies were compared with the federal TCM definition (2-day follow-up, 14-day visit, non-face-to-face services). We examined the associations of TCM billing, stroke center certification, and Magnet nursing excellence designation with TCM implementation., Results: Transitional care varied widely among 41 hospitals in North Carolina and no one strategy was universally applied or provided across hospitals. One third of hospitals met the TCM definition (37% provided telephone follow-up, 76% provided face-to-face provider follow-up, all provided a type of non-face-to-face support). There were no differences between groups (TCM met/not met) in hospital characteristics or transitional care resources and processes. Stroke center certification, Magnet designation, and use of TCM billing codes were not different for hospitals that did and did not meet the TCM definition., Conclusions: There was substantial variation in the provision of strategies supporting stroke patients' transition home from the hospital. Supportive stroke care transitions are essential when more than 50% of stroke patients are discharged home and more than half experience moderate to severe strokes. More research is needed to identify drivers of TCM uptake., Clinicaltrialsgov Identifier: NCT02588664., (© 2019 American Academy of Neurology.)

Background: Sex differences are known to exist in the management of older patients presenting with acute myocardial infarction (AMI). Few studies have examined the incidence and risk factors of AMI among young patients, or whether clinical management differs by sex., Methods: The Atherosclerosis Risk in Communities (ARIC) Surveillance study conducts hospital surveillance of AMI in 4 US communities (MD, MN, MS, and NC). AMI was classified by physician review, using a validated algorithm. Medications and procedures were abstracted from the medical record. Our study population was limited to young patients aged 35 to 54 years., Results: From 1995 to 2014, 28 732 weighted hospitalizations for AMI were sampled among patients aged 35 to 74 years. Of these, 8737 (30%) were young. The annual incidence of AMI hospitalizations increased for young women but decreased for young men. The overall proportion of AMI admissions attributable to young patients steadily increased, from 27% in 1995 to 1999 to 32% in 2010 to 2014 ( P for trend=0.002), with the largest increase observed in young women. History of hypertension (59% to 73%, P for trend<0.0001) and diabetes mellitus (25% to 35%, P for trend<0.0001) also increased among young AMI patients. Compared to young men, young women presenting with AMI were more often black and had a greater comorbidity burden. In adjusted analyses, young women had a lower probability of receiving lipid-lowering therapies (relative risk [RR]=0.87; 95% confidence interval [CI], 0.80-0.94), nonaspirin antiplatelets (RR=0.83; 95% CI, 0.75-0.91), beta blockers (RR=0.96; 95% CI, 0.91-0.99), coronary angiography (RR=0.93; 95% CI, 0.86-0.99) and coronary revascularization (RR = 0.79; 95% CI, 0.71-0.87). However, 1-year all-cause mortality was comparable for women versus men (HR=1.10; 95% CI, 0.83-1.45)., Conclusions: The proportion of AMI hospitalizations attributable to young patients increased from 1995 to 2014 and was especially pronounced among women. History of hypertension and diabetes among young patients admitted with AMI increased over time as well. Compared with young men, young women presenting with AMI had a lower likelihood of receiving guideline-based AMI therapies. A better understanding of factors underlying these changes is needed to improve care of young patients with AMI.

Background: Vascular age is an emerging health indicator and predictor of end-organ damage to the heart, brain, and kidney. Although there have been many review publications concerning risk factors for vascular aging, most include cross-sectional epidemiological studies, limiting inferences about temporality. There is a need for a review of longitudinal epidemiological studies with repeated measures of vascular structure and function to allow for a systematic examination of determinants of vascular age and the association of vascular aging with outcomes., Content: Arterial stiffness is the most frequently used measure of vascular aging. We report here results of an extensive literature review of longitudinal cohort studies with repeated measures of arterial stiffness to characterize determinants of vascular age. Additionally, we summarize population-based studies that have focused on the association of arterial stiffness with end-organ damage and adverse cardiovascular outcomes., Summary: Changes in arterial stiffness are evident in early childhood. In adults, arterial stiffness has been observed to progress at the average rate of 0.2 to 0.7 m/s for every 5 years of life. The state of the science is limited by the small number of studies with repeated measures of arterial stiffness and determinants of arterial stiffness progression, as well as limited studies in children and diverse race/ethnic groups. Several extant studies suggest that beyond age, cardiometabolic risk factors and adverse lifestyle behaviors contribute to arterial stiffening. Therefore, arterial stiffness is important in the assessment of healthy vascular aging and a possible target for the prevention of subclinical and clinical disease., (© 2018 American Association for Clinical Chemistry.)

The aging population routinely has comorbid conditions requiring complicated medication regimens, yet nonadherence can preclude optimal outcomes. This study explored the association of adherence in the elderly with demographic, socioeconomic, and disease burden measures. Data were from the fifth visit (2011-2013) for 6,538 participants in the Atherosclerosis Risk in Communities Study, conducted in four communities. The Morisky-Green-Levine Scale measured self-reported adherence. Forty percent of respondents indicated some nonadherence, primarily due to poor memory. Logit regression showed, surprisingly, that persons with low reading ability were more likely to report being adherent. Better self-reported physical or mental health both predicted better adherence, but the magnitude of the association was greater for mental than for physical health. Compared with persons with normal or severely impaired cognition, mild cognitive impairment was associated with lower adherence. Attention to mental health measures in clinical settings could provide opportunities for improving medication adherence.

Importance: The incidence of epilepsy is higher in older age than at any other period of life. Stroke, dementia, and hypertension are associated with late-onset epilepsy; however, the role of other vascular and lifestyle factors remains unclear., Objective: To identify midlife vascular and lifestyle risk factors for late-onset epilepsy., Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study is a prospective cohort study of 15 792 participants followed up since 1987 to 1989 with in-person visits, telephone calls, and surveillance of hospitalizations (10 974 invited without completing enrollment). The ARIC is a multicenter study with participants selected from 4 US communities. This study included 10 420 black or white participants from ARIC with at least 2 years of Medicare fee-for-service coverage and without missing baseline data. Data were analyzed betweeen April 2017 and May 2018., Exposures: Demographic, vascular, lifestyle, and other possible epilepsy risk factors measured at baseline (age 45-64 years) were evaluated in multivariable survival models including demographics, vascular risk factors, and lifestyle risk factors., Main Outcomes and Measures: Time to development of late-onset epilepsy (2 or more International Classification of Diseases, Ninth Revision codes for epilepsy or seizures starting at 60 years or older in any claim [hospitalization or outpatient Medicare through 2013]), with first code for seizures after at least 2 years without code for seizures., Results: Of the 10 420 total participants (5878 women [56.4%] and 2794 black participants [26.8%]; median age 55 years at first visit), 596 participants developed late-onset epilepsy (3.33 per 1000 person-years). The incidence was higher in black than in white participants (4.71; 95% CI, 4.12-5.40 vs 2.88; 95% CI, 2.60-3.18 per 1000 person-years). In multivariable analysis, baseline hypertension (hazard ratio [HR], 1.30; 95% CI, 1.09-1.55), diabetes (HR, 1.45; 95% CI, 1.17-1.80), smoking (HR, 1.09; 95% CI, 1.01-1.17), apolipoprotein E ε4 genotype (1 allele HR, 1.22; 95% CI, 1.02-1.45; 2 alleles HR, 1.95; 95% CI, 1.35-2.81), and incident stroke (HR, 3.38; 95% CI, 2.78-4.10) and dementia (HR, 2.56; 95% CI, 2.11-3.12) were associated with an increased risk of late-onset epilepsy, while higher levels of physical activity (HR, 0.90; 95% CI, 0.83-0.98) and moderate alcohol intake (HR, 0.72; 95% CI, 0.57-0.90) were associated with a lower risk. Results were similar after censoring individuals with stroke or dementia., Conclusions and Relevance: Potentially modifiable risk factors in midlife and the APOE ε4 genotype were positively associated with risk of developing late-onset epilepsy. Although stroke and dementia were both associated with late-onset epilepsy, vascular and lifestyle risk factors were significant even in the absence of stroke or dementia.

Purpose: The objectives of this study were to investigate sensitivity and specificity of myocardial infarction (MI) case definitions using multiple discharge code positions and multiple diagnosis codes when comparing administrative data to hospital surveillance data., Methods: Hospital surveillance data for ARIC Study cohort participants with matching participant ID and service dates to Centers for Medicare and Medicaid Services (CMS) hospitalization records for hospitalizations occurring between 2001 and 2013 were included in this study. Classification of Definite or Probable MI from ARIC medical record review defined "gold standard" comparison for validation measures. In primary analyses, an MI was defined with ICD9 code 410 from CMS records. Secondary analyses defined MI using code 410 in combination with additional codes., Results: A total of 25 549 hospitalization records met study criteria. In primary analysis, specificity was at least 0.98 for all CMS definitions by discharge code position. Sensitivity ranged from 0.48 for primary position only to 0.63 when definition included any discharge code position. The sensitivity of definitions including codes 410 and 411.1 were higher than sensitivity observed when using code 410 alone. Specificity of these alternate definitions was higher for women (0.98) than for men (0.96)., Conclusion: Algorithms that rely exclusively on primary discharge code position will miss approximately 50% of all MI cases due to low sensitivity of this definition. We recommend defining MI by code 410 in any of first 5 discharge code positions overall and by codes 410 and 411.1 in any of first 3 positions for sensitivity analyses of women., (Copyright © 2018 John Wiley & Sons, Ltd.)

Background: Previous studies suggest that heart failure (HF) is an independent risk factor for cognitive decline. A better understanding of the relationship between HF, cognitive status, and cognitive decline in a community-based sample may help clinicians understand disease risk., Objective: To examine whether persons with HF have a higher prevalence of cognitive impairment and whether persons developing HF have more rapid cognitive decline., Design: This observational cohort study of American adults in the Atherosclerosis Risk in Communities (ARIC) study has two components: cross-sectional analysis examining the association between prevalent HF and cognition using multinomial logistic regression, and change over time analysis detailing the association between incident HF and change in cognition over 15 years., Participants: Among visit 5 (2011-2013) participants (median age 75 years), 6495 had neurocognitive information available for cross-sectional analysis. Change over time analysis examined the 5414 participants who had cognitive scores and no prevalent HF at visit 4 (1996-1998)., Measurements: The primary outcome was cognitive status, classified as normal, mild cognitive impairment [MCI], and dementia on the basis of standardized cognitive tests (delayed word recall, word fluency, and digit symbol substitution). Cognitive change was examined over a 15-year period. Control variables included socio-demographic, vascular, and smoking/drinking measures., Results: At visit 5, participants with HF had a higher prevalence of dementia (adjusted relative risk ratio [RRR] = 1.60 [95% CI 1.13, 2.25]) and MCI (RRR = 1.36 [1.12, 1.64]) than those without HF. A decline in cognition between visits 4 and 5 was - 0.07 standard deviation units [- 0.13, - 0.01] greater among persons who developed HF compared to those who did not. Results did not differ by ejection fraction., Conclusion: HF is associated with neurocognitive dysfunction and decline independent of other co-morbid conditions. Further study is needed to determine the underlying pathophysiology.

Purpose: Despite well-documented associations of socioeconomic status with incident heart failure (HF) hospitalization, little information exists on the relationship of socioeconomic status with HF diagnosed in the outpatient (OP) setting., Methods: We used Poisson models to examine the association of area-level indicators of educational attainment, poverty, living situation, and density of primary care physicians with incident HF diagnosed in the inpatient (IP) and OP settings among a cohort of Medicare beneficiaries (n = 109,756; 2001-2013)., Results: The age-standardized rate of HF incidence was 35.8 (95% confidence interval [CI], 35.1-36.5) and 13.9 (95% CI, 13.5-14.4) cases per 1000 person-years in IP and OP settings, respectively. The incidence rate differences (IRDs) per 1000 person-years in both settings suggested greater incidence of HF in high- compared to low-poverty areas (IP IRD = 4.47 [95% CI, 3.29-5.65], OP IRD = 1.41 [95% CI, 0.61-2.22]) and in low- compared to high-education areas (IP IRD = 3.73 [95% CI, 2.63-4.82], OP IRD = 1.72 [95% CI, 0.97-2.47])., Conclusions: Our results highlight the role of area-level social determinants of health in the incidence of HF in both the IP and OP settings. These findings may have implications for HF prevention policies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Modification of guideline-directed medical therapy (GDMT) in hospitalized patients with heart failure (HF) has not been extensively evaluated., Methods: The community surveillance arm of the Atherosclerosis Risk in Communities Study identified 6959 HF hospitalizations from 2005-2011. Predictors of GDMT modification and survival were assessed using multivariable logistic regression and Cox proportional hazards models., Results: For 5091 hospitalizations, patient mean age was 75 years, 53% were female, 69% were white, and 81% had acute decompensated heart failure (ADHF). Regarding ejection fraction (EF), 31% of patients had HF with reduced EF (HFrEF), 24% had HF with preserved EF (HFpEF), and 44% were missing EF values. At admission, 52% of patients received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), 66% β-blockers (BBs), 9% aldosterone-receptor antagonists, 16% digoxin, 10% hydralazine, and 29% nitrates. Modification of GDMT occurred in up to 23% of hospitalizations. Significant predictors of GDMT initiation included ADHF and HFrEF; discontinuation of medications was observed with select comorbidities. In HFrEF, initiation of any GDMT was associated with reduced 1-year all-cause mortality (adjusted hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.23-0.71) as was initiation of ACEI/ARBs, BBs, and digoxin. Discontinuation of any therapy versus maintaining GDMT was associated with greater mortality (HR 1.30, 95% CI 1.02-1.66). Similar trends were observed in HFpEF., Conclusions: Our study suggests that GDMT initiation is associated with increased survival, and discontinuation of therapy is associated with reduced survival in hospitalized patients with HF. Future studies should be conducted to confirm the impact of GDMT therapy modification in this population., (© 2018 Pharmacotherapy Publications, Inc.)

Objective: Vital exhaustion (VE), a construct defined as lack of energy, increased fatigue and irritability, and feelings of demoralisation, has been associated with cardiovascular events. We sought to examine the relation between VE and sudden cardiac death (SCD) in the Atherosclerosis Risk in Communities (ARIC) Study., Methods: The ARIC Study is a predominately biracial cohort of men and women, aged 45-64 at baseline, initiated in 1987 through random sampling in four US communities. VE was measured using the Maastricht questionnaire between 1990 and 1992 among 13 923 individuals. Cox proportional hazards models were used to examine the hazard of out-of-hospital SCD across tertiles of VE scores., Results: Through 2012, 457 SCD cases, defined as a sudden pulseless condition presumed due to a ventricular tachyarrhythmia in a previously stable individual, were identified in ARIC by physician record review. Adjusting for age, sex and race/centre, participants in the highest VE tertile had an increased risk of SCD (HR 1.48, 95% CI 1.17 to 1.87), but these findings did not remain significant after adjustment for established cardiovascular disease risk factors (HR 0.94, 95% CI 0.73 to 1.20)., Conclusions: Among participants of the ARIC study, VE was not associated with an increased risk for SCD after adjustment for cardiovascular risk factors., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)