Introduction: Older adults in rural areas face elevated chronic disease risk and greater barriers to physical activity (PA). We determined how PA patterns vary across the rural-urban spectrum using the Rural Urban Commuting Area (RUCA) 4-category system, incorporating a broad set of demographic and health variables. Hypothesis: Rural residents would engage in less moderate-to-vigorous physical activity (MVPA) and sedentary behavior (SB), but more light-intensity physical activity (LIPA) compared to urban residents. Methods: Accelerometer data (Actical™) from REGARDS participants collected between 2009 and 2013 were analyzed across RUCA category: isolated, small rural, large rural, and urban. PA was categorized into three intensity domains based on activity counts per minute (CPM): SB (<50), LIPA (50–1064), and MVPA (≥1065). Multivariable general linear models identified education and income as significant PA determinants, which were retained in fully adjusted linear regression models. Models were sequentially adjusted for wear time, demographic and socioeconomic factors, and health-related covariates. Interaction terms were tested for effect modification of covariates on rurality and SB, LIPA, and MVPA. Results: Of the 30,239 Black and White adults aged ≥45 years enrolled in REGARDS between 2003 and 2007, 8,098 had accelerometer data, and 7,317 had valid RUCA Classification ( Table ). Urban residents engaged in the most SB (691 min/d) and least LIPA (188 min/d) ( Figure) . Compared to urban residents, those in isolated and small rural areas engaged in significantly more LIPA and less SB ( Table ). MVPA levels were low across all RUCA groups (avg 13.1 min/d), with no statistically significant group differences. A significant interaction was observed between education and RUCA category for LIPA (p= 0.03). Individuals in small rural areas with less than a high school education engaged in significantly more LIPA than urban residents with a college education (estimate = 46.65 min/d, p=0.0014). Conclusions: We observed uniformly low levels of MVPA across all RUCA categories. Rural–urban differences in overall PA were more strongly influenced by variations in LIPA and SB. These patterns underscore the role of income, education, and environmental context in shaping physical activity disparities. It remains unclear whether shared barriers contribute to low MVPA across RUCA classes or whether distinct factors promote higher LIPA in certain rural populations.

Background: Younger age at menopause (premature and early menopause) occurs more often in Black women than in White women and is associated with an increased cardiovascular disease risk. Traditional risk factors for early onset are well studied, but the role of adverse childhood experiences (ACEs) is unclear. This study examined the association between ACEs and age at menopause. We hypothesized that women reporting ACEs are more likely to experience menopause at younger ages compared to those reporting no ACEs. Methods: A cross-sectional analysis was conducted in 4,491 Black and White women aged 45 years from the REasons for Geographic and Racial Differences in Stroke Study. ACEs were assessed in the Childhood and Family Life Factors ancillary study using the Childhood SES Factors questionnaire and categorized into groups (0, 1, 2-3, and 4+ ACEs) for analyses. Age at menopause was measured as the self-reported age at last menstrual period, and categorized as premature (<40), early (40- 45), normal (45- 55), and late menopause (>55). Multinomial logistic regression was used to estimate separate odds ratios (OR) and 95% confidence intervals (CI) for early, premature, and late versus normal menopause. A crude (model 1) and four sequentially adjusted models, for demographic (model 2), socioeconomic (model 3), behavioral (model 4), and reproductive (model 5) covariates, were fit. Results: Women were primarily White (70%), with a mean age at menopause of 45.6 years (± 8.1). Most women (58%) experienced a normal age at menopause, whereas 22% experienced premature, 14% experienced early, and 6% experienced late menopause. Approximately 22% reported 1 ACE, 24% reported 2-3 ACEs, and 7% reported 4+ ACEs. Reporting 2–3 ACEs (versus no ACEs) was associated with higher odds of premature menopause (fully adjusted OR [95% CI] = 1.33 [1.09–1.63]) and early menopause (fully adjusted OR [95% CI] = 1.32 [1.03–1.69]). Reporting ≥4 ACEs (versus no ACEs) was associated with higher odds of premature menopause in models 1-4 (model 4 OR [95% CI] = 1.65 [1.22–2.22], but this effect was attenuated in the fully adjusted model. No associations were observed for late menopause. Conclusion: Women with 2–3 ACEs were more likely to experience premature and early menopause, while associations for ≥4 ACEs with premature were inconsistent. Further research is needed to understand how ACEs contribute to differences in reproductive aging and menopause timing.

BACKGROUND:Despite the health benefits of parental leave (PL), many physicians in the United States take little to no PL. This issue is particularly pressing in academic neurology, which faces high burnout rates and a projected shortage. This study evaluated the impact of PL on career achievements and burnout in academic neurology. METHODS:A cross-sectional survey of neurologists in 19 U.S. institutions measured PL experience, academic achievements, and burnout. Chi-squared test was used to assess for group differences in the two groups: PL/NoPL and in subgroups: men/women. General linear regression models were used to examine the association between PL, gender, achievements, and burnout. RESULTS:Among 239 respondents with children, 74.8% of women and 28.6% of men took PL (87.9% of women and 97.3% of men took less than 6 weeks). Academic achievement measures were similar for those who took PL and those who did not (NoPL) with the exception of fewer awards in the PL group (mean 2.25 for PL and 6.21 for NoPL, p = 0.018). The PL group showed higher family-work conflict score (PL-score = 22.64, NoPL-score = 18.27, p < 0.001) and higher emotional exhaustion (PL 43.2%, NoPL 34.6%, p = 0.017) than the NoPL group. Emotional exhaustion was higher in women compared with men, despite higher weekly work hours in the PL group men (p = 0.021). CONCLUSION:Faculty who took PL did not have worse academic productivity compared with NoPL. But the PL group had higher levels of burnout and emotional exhaustion, especially in women, highlighting the need for support during and when returning from PL.

Background Atrial fibrillation (AF) is the most common arrhythmia. Although it was recently identified as a risk factor for coronary heart disease (CHD), the underlying pathophysiology is not well understood. Biomarkers could provide insights on underlying mechanisms and identify potential predictors of CHD among people with AF. Methods The REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort study enrolled 30 239 White and Black adults aged 45 and older in 2003 to 2007. Among those with baseline AF and no history of stroke or CHD, 13 cardiovascular risk biomarkers were measured at baseline. We calculated hazard ratios (HR) for incident CHD by biomarkers using Cox proportional hazards model adjusting for risk factors and use of statins, aspirin, and anticoagulants. Results Among 1818 participants with prevalent AF mean age was 69 years (SD 10 years). There were 201 (11%) cases of incident CHD over 9 years. Several biomarkers were associated with incident CHD: NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), GDF‐15 (growth differentiation factor 15), C‐reactive protein, interleukin‐6, D‐dimer, cholesterol, lipoprotein(a), triglycerides, low‐density lipoprotein, and gamma‐glutamyl transferase, with HRs 1.17 to 1.69 per SD increment. There were no associations for Factor VIII, galectin 3, and high‐density lipoprotein. The largest associations were for NT‐proBNP and GDF‐15 with respective HRs per SD 1.69 (95% CI, 1.42–2.01) and 1.45 (95% CI, 1.21–1.74). Comparing the top versus bottom tertile, the largest associations were NT‐proBNP (HR 3.14 [95% CI 2.03–4.84]), interleukin‐6 (HR, 2.69 [95% CI, 1.78–4.06]), and GDF‐15 (HR, 2.20 [95% CI, 1.38–3.51]). Conclusions Multiple biomarkers were associated with incident CHD in AF with the largest associations being myocardial strain and inflammation.

Abstract Background and aims Individual-level social factors are disproportionately associated with stroke for women, but the association between structural sexism (SS) and stroke is unclear. Methods Individuals from the nationwide REGARDS study without stroke were included (n=27,881) during 2003-2007 and followed for stroke or death until September 30, 2022. Using data listed in Table 1, SS was calculated as a sum score of inequalities between women and men across multiple social determinants of health at the county or state level and linked to REGARDS participants. Associations between SS and its subdomains with stroke for each sex, accounting for the competing risk of death and clustering of individuals within counties, were assessed by sex-stratified Fine-Gray models with robust sandwich estimators. Models were adjusted for covariates listed in Table 2. An interaction between SS and sex was added to an unstratified model. Results Over a median 12.5-year follow-up, 1,793 individuals (mean age=64.6 years, 55.5% women) had incident stroke. SS was associated with increased stroke rates (HR=1.05, 95% CI 0.97, 1.13 per one standard deviation increase in SS) among women and decreased stroke rates (HR=0.92, 95% CI 0.85, 0.99) among men (interaction p-value=0.01). For subdomains of SS (Table 2), socioeconomic inequality was associated with increased stroke rates (HR=1.15, 95% CI 1.04, 1.28) among women, and conservative religion was associated with decreased stroke rates (HR=0.86, 95% CI 0.76, 0.97) among men. Conclusions Findings suggest the potentially harmful impact of SS on stroke risk among women. Future studies should aim to unravel the underlying mechanisms of this association. Conflict of interest Chen Chen. nothing to disclose. Virginia Howard. nothing to disclose. Natalie Colabianchi. nothing to disclose. Debora Kamin Mukaz. nothing to disclose. Lynda Lisabeth. nothing to disclose. Table 1 - belongs to Methods Table 2 - belongs to Results

INTRODUCTION: The study aims to investigate associations between markers of atrial cardiopathy and cognitive function trajectories in adults without prior AF. METHODS: The study included 4,486 participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Markers of atrial cardiopathy included atrial premature complexes and N-Terminal pro-Brain Natriuretic Peptide (NT pro-BNP). Cognitive status was measured using the Six-Item Screener (SIS). Cognitive status trajectories were identified using latent class growth models. RESULTS: Three unique cognitive trajectories over the 8-year follow-up were identified: 86.7% showed a normal and stable trajectory of SIS score, 7.6% showed a progressively decreasing trajectory, and 5.7% showed a dramatic decreasing trajectory. Age, black participants, and antidepression drugs were significantly associated with the “dramatic decrease” trajectory. Elevated NT pro-BNP was significantly associated with the “dramatic decrease” trajectory. DISCUSSION: Markers of left atrial cardiopathy may have implications for early diagnosis and prevention of cognitive impairment.

Background: Sedentary behavior (SB) has been associated with the risk of cardiovascular disease, independent of physical activity (PA) and sleep. However, the effect of replacing SB with PA or sleep on atrial fibrillation (AF) risk remains unclear. Methods: This study included participants from the UK Biobank who wore wrist-worn accelerometers for seven days consecutively in 2013-2015. Those with prevalent AF, insufficient wearing time, and invalid or uncalibrated accelerometry data were excluded. Daily time spent in light PA (LPA), moderate to vigorous PA (MVPA), sedentary behavior (SB), and sleep were derived from accelerometer recordings, based on a previously trained and validated machine learning model in UK sample. Incident AF was classified by at least 1 ICD-10 code for the condition listed as either a primary diagnosis, secondary diagnosis, or cause of death through hospital and death registry data linkage (I48.x). Follow up began at accelerometer assessment and continued until the earliest of AF onset, loss to follow-up, death, or study censoring date. Using the proportional hazard model, isotemporal substitution was applied to examine the effect of replacing 30 minutes of SB with equivalent durations of each type of PA and sleep on AF risk, adjusting for demographic, socioeconomic, behavioral, and clinical covariates. Stratified analyses by sex and age (<65 vs. ≥65 years) were performed. Results: Among 86,101 participants (57% female, mean age 56±7.8 years, 97% White race), 4,040 AF cases were identified during a median of 7.9 years of follow-up. On average, participants spent 9.0 ± 1.9 hours in SB, 4.8 ± 1.3 hours in LPA, 0.7 ± 0.6 hours in MVPA, and 8.5 ± 1.3 hours in sleep per day. Replacing 30 minutes of SB with PA was associated with a slightly lower risk of AF in the model adjusted for age, sex, race and ethnicity, and assessment centers [LPA: HR 0.98, 95% CI (0.97, 0.99); MVPA: HR 0.89, 95% CI (0.87, 0.92)]. The associations were attenuated after full adjustment [LPA: HR 1.00, 95% CI (0.99, 1.02); MVPA: HR 0.98, 95% CI (0.95, 1.02)]. Results were consistent across sex and age strata. No association with sleep was observed when substituting SB with sleep. Conclusion: In a large population-based cohort in the UK, substituting SB with other daily activities or sleep did not reduce AF risk after accounting for confounding factors. Whether these findings are generalizable to more diverse populations warrant further investigation.

Background: As of mid-2025, over 100 million people have had COVID-19 and in the United States, 1.2 million have died. Black Americans continue to experience higher rates of severe COVID-19 (requiring hospitalization or causing death) than White Americans. Biological mechanisms underlying severe COVID-19 remain unclear, although evidence suggests endothelial dysfunction contributes to disease severity. Aims: We studied associations of pre-pandemic endothelial biomarkers with severe COVID-19 and evaluated differences in associations between Black and White Americans. Methods: We employed a case only design among Black and White participants of the REasons for Geographic and Racial Differences in Stroke (REGARDS) study who had COVID-19 between 2020 and 2021. Endothelial biomarkers (E-selectin, P-selectin, factor VIII, ICAM-1, and VCAM-1) were measured from stored serum collected in 2013-2016. The outcome was severe COVID-19 defined as hospitalization or death (adjudication rate 96.2%). Non-severe COVID-19 (the reference group) was defined as self-reported symptomatic COVID-19, positive SARS-CoV2 testing, and no hospitalization or death. Logistic regression was used to estimate odds ratios of severe COVID-19 by SD higher of each biomarker. Restricted cubic splines were used to visualize odds ratios of severe COVID-19. Results: Among the 415 participants with COVID-19, 47% were male, 33% were Black, and the mean (SD) age was 60 (7) years. Each SD higher ICAM-1 and log VCAM-1, but not other biomarkers, was associated with 30% higher odds of severe COVID-19 ( Table ). Associations were similar across racial groups ( Table ). Restricted cubic splines showed that the association of VCAM-1 and severe COVID-19 was non-linear whereas the association of ICAM-1 and severe COVID-19 was linear ( Figure ). Conclusions: Pre-pandemic endothelial dysfunction, reflected by higher ICAM-1 and VCAM-1, was associated with higher odds of severe COVID-19. These findings suggest that longstanding endothelial dysfunction predisposes to more severe COVID-19, and highlights ICAM-1 and VCAM-1 as potential therapeutic targets. Replication in larger studies is needed to confirm these results.

Introduction: A best practice for sleep actigraphy assessment includes concurrent participant completion of a daily sleep log, which poses additional burden on both the participant (~3 minutes [min]/day) and research staff (~30 min/participant for data entry and verification steps). The Heuristic algorithm looking at the Distribution of Change in Z-angle (HDCZA), the default GGIR algorithm in R, estimates the rest interval by detecting sleep onset and wake-up times from raw acceleration data, without a sleep log. This study examined equivalence in HDCZA versus log-guided sleep parameters. Methods: Data are from an initial sub-set of 1,059 REGARDS 24H-ACT ancillary study participants (aged 77.7 ± 6.9 years, 56.9% female, 23.2% Black, and 52.6% from the Stroke Belt region). Participants were asked to wear a GENEActiv device (Activinsights Ltd.; Kimbolton, UK) on their non-dominant wrist for 24 hours/day over 8 consecutive days. Raw acceleration data were processed in GGIR using HDCZA- and log-guided approaches. A set of primary sleep parameters, including sleep onset and wake-up times (hh:mm ± min; 24H time) and rest and sleep intervals (min), were averaged across nights and compared between the two scoring methods using paired t-tests and two one-sided equivalence tests with ± 30 min equivalent zones. Results: The (mean ± standard deviation) sleep onset time was (HDCZA: 22:54 ± 106.5 min vs log: 22:50 ± 94.0 min), wake-up time was (HDCZA: 7:07 ± 103.4 min vs log: 7:18 ± 91.9 min), rest interval was (HDCZA: 493.5 ± 101.2 min vs log: 507.7 ± 88.6 min), and sleep interval was (HDCZA: 411.6 ± 91.7 min vs log: 366.8 ± 79.5 min). The mean difference in sleep onset time was statistically null; however, wake-up time, rest, and sleep interval durations significantly differed between the scoring methods (all p<0.001). The sleep interval duration was not statistically equivalent between scoring methods; however, the remaining sleep parameters were statistically equivalent within ± 30 min (Figure). Conclusion: While statistical equivalence was found with some sleep parameters, the HDCZA method did not yield precise estimates for the sleep interval. Given the importance of accurate sleep interval estimation for public health recommendations and analytic techniques based on sleep duration (e.g., compositional data analysis), using only the HDCZA-detected method may lead to misclassification of overall sleep health. Funding: RF1AG077707 and R01AG077707 (to KMD, KPG, and PP)

RATIONALE: Chronic lower respiratory diseases (CLRD) confer higher risks from respiratory viral infections, hence CLRD patients are prioritized for influenza, pneumococcal, and COVID-19 vaccination. Nonetheless, vaccine deferral and declination remain common. Given that COVID-19 vaccination is particularly polarizing, and attitudes toward it may differ from other vaccines, we assessed COVID-19 vaccination behaviors and attitudes in adults with versus without CLRD and/or smoking history, which is strongly associated with CLRD risk. METHODS: We pooled data from 10 cohorts participating in the Collaborative Cohort of Cohorts for COVID-19 Research (C4R) that collected pre-pandemic data on self-reported physician diagnosis of asthma or COPD. C4R assessed COVID-19 vaccination status through three waves of standardized questionnaires (2020-2022, 2021-2023, 2023-2024). Prompt COVID-19 vaccination was defined as self-report of receiving at least one COVID-19 vaccine by May 1, 2021. Cumulative COVID-19 vaccine count was self-reported on the Wave 3 Questionnaire. Vaccine attitudes and receipt of influenza and/or pneumococcal vaccines were self-reported on the Wave 1 or 2 Questionnaire. Age-adjusted Poisson regression was used to test associations of vaccination behaviors with CLRD and smoking status at the most recent pre-pandemic exam. RESULTS: Of 20,034 participants (pre-pandemic COPD, 9.3%; asthma, 11.7%; current smoking, 13.4%; former smoking, 36.3%), 64.2% reported prompt COVID-19 vaccination. Among the subset of 10,626 participants completing the Wave 3 Questionnaire in 2023-24, the median COVID-19 vaccine count was 3 (Q1:2, Q3:4). Compared to participants without CLRD, prompt vaccination was more likely in those with asthma (RR=1.04, 95%CI:1.01-1.07, p=0.008) and less likely with COPD (RR=0.94, 95%CI:0.91-0.98, p=0.001), but there were no differences in doses for asthma and COPD. Compared to never smokers, former smoking participants were more likely to receive prompt vaccination (RR=1.11, 95%CI:1.08-1.13, p<0.0001) and more vaccine doses (RR=1.03, 95%CI:1.01-1.05, p=0.015); conversely, current smoking was inversely associated with prompt vaccination (RR=0.94, 95%CI:0.91-0.97, p=0.001) and was associated with fewer doses (RR=0.93, 95%CI:0.89-0.96, p<0.0001). Participants with CLRD versus without CLRD were more likely to report receiving influenza and pneumococcal vaccines, but they were more likely to believe that vaccines are unsafe or ineffective (figure). CONCLUSIONS: COPD was associated with lower likelihood of prompt COVID-19 vaccination. Current smoking was associated with both lower likelihood of prompt COVID-19 vaccination and a lower number of COVID-19 vaccine doses by 2023-24. These associations may be partly attributed to negative vaccine attitudes and beliefs. How the COVID-19 pandemic may have influenced vaccine behaviors and attitudes merits additional study.

Background: Hypertension remains a significant public health concern, with persistent racial and gender disparities in disease burden. Residential segregation limits people’s access to resources that could promote health. We sought to investigate racial and gender differences in the association of residential segregation and risk of incident hypertension. Methods: This analysis included Black and White participants of the REasons for Geographic And Racial Differences in Stroke study (30,239 Black and White adults from the 48 contiguous US states) who did not have hypertension at the first visit (2003-7) and completed the 2 nd visit (2013-16). County-level residential segregation was measured with the delta index, where higher scores indicate greater racial segregation. The delta index measures the concentration dimension, which depicts the relative amount of space occupied by Black people in an area. Modified Poisson regression was used to calculate risk ratios (RRs) of incident hypertension per 1-standard deviation (SD) increment delta index. Models were adjusted for age, gender, and systolic blood pressure. Racial and gender differences in the association of the delta index and hypertension risk were tested. Results: Among the 6,894 participants, the mean (SD) age was 62 (8.4) years. The incidence of hypertension was 48% for Black women, 43% for Black men, 32% White women, and 34% White men. The risk of hypertension was 3% lower for each SD higher delta index (RR: 0.97; 95% [confidence interval] CI: 0.94-0.99). There were significant racial and gender differences in the association of the delta index and hypertension risk (Table). Black women had a 9% lower risk of hypertension per SD higher delta index (RR: 0.91; 95% CI: 0.85-0.96). The association was not significant for the other race-gender groups. Conclusions: Our findings revealed that delta index was associated with lower risk of hypertension in Black women. Given that previous research generally reports positive associations between residential segregation and health outcomes, we need to investigate mechanisms in segregated areas that explain this negative association between the delta index and hypertension risk.

Background: Loneliness is a growing public health concern. In 2022, the AHA identified it as a contributor to poor cardiovascular health, followed by a 2023 U.S. Surgeon General advisory declaring an “Epidemic of Loneliness and Isolation”. Although linked to mortality, its independent effect and generalizability across diverse groups remain understudied. With over half of U.S. adults reporting loneliness, understanding its role may be essential to improving cardiovascular outcomes. Research Questions/Hypothesis: We examined the association between loneliness and CVD mortality in a diverse national cohort. We hypothesized that loneliness would be associated with increased CVD mortality. Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study is a prospective cohort of 30,239 adults aged ≥45 years recruited from 2003-2007. We included those who completed a baseline loneliness item assessing feelings in the past week. Cox proportional hazards models estimated HRs and 95% CIs for the association between loneliness and time to CVD death. Models were sequentially adjusted for demographics (age, race, gender), SDOH (employment, education, income, insurance, region, poverty, health professional shortage, public health infrastructure), clinical factors (hypertension, diabetes, self-rated physical health, obesity, inflammation, cognition), health behaviors (smoking, activity, diet, medication adherence), and objective social health (partnership, social isolation, social support). Effect modification by age, race, and gender was assessed using interaction terms. Results: We included 29,387 participants with median follow-up of 13.1 years (IQR 7.3-16.1). Mean age was 65.0 years (SD 9.4); 41% identified as Non-Hispanic Black and 55% were women. Overall, 21% of participants reported loneliness in the past week, with 3,643 CVD deaths observed. Loneliness was associated with a 41% increased hazard of CVD mortality in unadjusted models (HR, 1.41; 95% CI, 1.31-1.53). The association attenuated but remained significant in the fully adjusted model (HR, 1.21; 95% CI, 1.03-1.41). No effect modification was observed. Conclusion: Loneliness was associated with increased CVD mortality risk, even after accounting for clinical, behavioral, and social factors. A one-time, self-reported loneliness measure may serve as a practical tool for identifying at-risk patients and inform efforts to reduce cardiovascular risk.

Importance:SARS-CoV-2 infection has been linked to neurotoxic effects and cognitive deficits. Objective:To determine whether decreases in cognitive function were accelerated after SARS-CoV-2 infection compared with individuals not infected. Design, Setting, and Participants:Multicenter, prospective cohort study from 2016 to 2022 among 3525 participants alive on March 1, 2020, and enrolled in The Atherosclerosis Risk in Communities (ARIC) study and the Collaborative Cohort of Cohorts for COVID-19 Research study who completed a prepandemic cognitive assessment and a pandemic-era assessment of SARS-CoV-2 infection. Final analyses performed in November 2024. Exposure:SARS-CoV-2 infection determined via self-report of a positive SARS-CoV-2 test or health care professional diagnosis of COVID-19, a positive SARS-CoV-2 antinucleocapsid antibody response, or presence of an administrative code for COVID-19 on medical records. Main outcomes and measures:A neuropsychological battery assessed multiple cognitive domains, and a cocalibrated confirmatory factor analysis generated factor scores for global cognitive function. The primary outcome was the rate of excess change in cognitive function. Results:The 3525 eligible participants had a mean (SD) age of 80.8 (4.7) years, 2085 (59.1%) were female, 752 (21.4%) were Black, and 2773 (78.6%) were White. SARS-CoV-2 infection was detected among 307 participants (8.7%), 103 of whom (33.6%) were hospitalized. Among uninfected participants, the mean annualized change in cognitive function was -0.09 (95% CI, -0.13 to -0.04). Compared with this rate, change was faster (β = -0.06; 95% CI, -0.09 to -0.02) among participants hospitalized for infection, but not different from participants who were infected but not hospitalized (β = 0.00; 95% CI, -0.02 to 0.03). The association among participants hospitalized for infection was evident in the cognitive domains of memory and executive function, but not language. Conclusions and relevance:This cohort study of older participants found accelerated decreases in cognition among individuals hospitalized for SARS-CoV-2 infection, but not nonhospitalized infection, in comparison with individuals not yet infected.

BACKGROUND Black US adults experience a greater hypertension burden and have lower levels of soluble receptors for advanced glycation end products (sRAGE). sRAGE may reduce inflammation, which is itself a hypertension risk factor. We hypothesized that higher sRAGE levels are associated with a lower risk of incident hypertension in a cohort of Black and White adults. METHODS The REasons for Geographic and Racial Differences in Stroke (REGARDS) enrolled 30,239 Black and White adults from the contiguous United States in 2003-2007; a second visit occurred in 2013-2016. sRAGE was measured at baseline by ELISA in 4,400 participants attending both visits. Hypertension was defined as BP > 140/90 mm Hg or use of antihypertensive medications. Participants with baseline hypertension were excluded. Poisson regression estimated incident hypertension risk ratios (RR) by sRAGE levels, adjusting for confounders. RESULTS Among 1,799 participants without baseline hypertension (mean [SD] age 62 [8] years, 55% females, 25% Black), 46% of Black participants and 31% of White participants developed hypertension. Median sRAGE was lower in Black than White persons (P < 0.0001). Relative to quartile 1, White participants in quartile 4 of sRAGE had a 24% lower risk of incident hypertension (RR 0.76; 95% CI 0.59, 0.96) in a minimally adjusted model, but no differences in a fully adjusted model (0.81; 0.63 to 1.05). There was no association of sRAGE with hypertension in Black participants. CONCLUSIONS Higher baseline sRAGE levels were not associated with lower risk of incident hypertension after adjusting for known confounders. Low sRAGE might represent adverse inflammation that drives hypertension rather than being a primary driver of hypertension development itself.

Background: Rural populations in the United States face shorter life expectancies and higher cardiovascular mortality compared to urban populations. Understanding how the American Heart Association’s Life’s Essential 8 (LE8) metrics vary across urban and rural populations may assist in designing interventions to address cardiovascular health (CVH) among rural adults. Hypothesis: We hypothesized rural adults would have worse CVH, as measured by LE8, compared to urban and suburban adults. Methods: REGARDS is a national cohort of Black and White adults age 45 and older, enrolled from 2003-7. Data from participants who completed the home visit (2013–2016) and were not missing data on LE8 metrics were used for the present analysis. LE8 metrics were assessed through questionnaires, physical measurements, and lab data. The 2010 Rural-Urban Commuting Area (RUCA-7) codes were used to classify population density. Mean LE8 scores and individual metrics were examined across 7 RUCA classes ( isolated rural, other small rural, small rural core, other large rural, large rural core, other urban, and urban core ), using general linear modeling, adjusting for demographic characteristics, income, and education. Results: A total of 8,162 REGARDS participants were included in the present analysis. The majority resided in Urban Core areas (73.6%). REGARDS participants' distribution across the RUCA class was similar to the US Census data. (Table 1) Adjusting for demographic factors, LE8 scores increased with increasing urbanicity, with Other Small Rural and Isolated Rural areas having the lowest LE8 scores. Modest attenuation was observed after further adjustment for education and income. (Figure 1) No interactions by race or sex were observed. Individual LE8 metrics for diet, blood pressure, and blood glucose demonstrated similar trends across RUCA class, with improved metrics associated with increased urbanicity. Metrics for lipids, sleep, and smoking metrics did not differ by RUCA class. Conclusion: In this large cohort of adults from 48 contiguous US states, higher urbanicity was associated with higher mean LE8 scores, reflecting better CVH. This association with improved CVH was driven by better diet, blood pressure, and blood glucose scores. Understanding population-level differences in CVH across the country will inform the development of interventions to address poor CVH in rural populations.