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Background: It is unknown how blood pressure (BP) relates to stroke risk across levels of hypertension daily dose (HDD)-quantified antihypertensive medication intensity., Methods and Results: The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study enrolled 30 239 participants from the 48 contiguous US states in 2003 to 2007 with in-person follow-up in 2013 to 2016 (Visit 2). We included those without prior stroke at Visit 2, treating this visit as T 0 . Biannual phone calls and medical record review ascertained incident stroke events. Cox proportional hazard models estimated the hazard ratio (HR) of incident stroke by treatment intensity defined by systolic BP stages and HDD groupings. There were 344 stroke events over a median 5.5 years. Relative to systolic BP <120 mm Hg and no antihypertensive medications, the stroke HR was 2.86 (95% CI, 1.68-4.85) for systolic BP 140 to 159 mm Hg and HDD tertile 2, 2.33 (1.37-3.97) for systolic BP 140 to 159 mm Hg and HDD tertile 3, 3.08 (1.20-7.88) for systolic BP ≥160 mm Hg and HDD tertile 2, and 3.66 (1.61-8.30) for systolic BP ≥160 mm Hg and HDD tertile 3. Stroke risk was similar across HDD levels for people with systolic BP <140 mm Hg., Conclusions: Among adults without prior stroke, systolic BP ≥140 mm Hg and HDD tertile ≥2 was associated with greater stroke risk. For adults with BP <140 mm Hg, stroke risk was similar despite cumulative dose of antihypertensive medications used. These findings support the practice of BP-lowering medications to mitigate stroke risk.

Objectives: To investigate associations between health-related behaviors as measured using the Brain Care Score (BCS) and neuroimaging markers of white matter injury., Methods: This prospective cohort study in the UK Biobank assessed the BCS, a novel tool designed to empower patients to address 12 dementia and stroke risk factors. The BCS ranges from 0 to 21, with higher scores suggesting better brain care. Outcomes included white matter hyperintensities (WMH) volume, fractional anisotropy (FA), and mean diffusivity (MD) obtained during 2 imaging assessments, as well as their progression between assessments, using multivariable linear regression adjusted for age and sex., Results: We included 34,509 participants (average age 55 years, 53% female) with no stroke or dementia history. At first and repeat imaging assessments, every 5-point increase in baseline BCS was linked to significantly lower WMH volumes (25% 95% CI [23%-27%] first, 33% [27%-39%] repeat) and higher FA (18% [16%-20%] first, 22% [15%-28%] repeat), with a decrease in MD (9% [7%-11%] first, 10% [4%-16%] repeat). In addition, a higher baseline BCS was associated with a 10% [3%-17%] reduction in WMH progression and FA decline over time., Discussion: This study extends the impact of the BCS to neuroimaging markers of clinically silent cerebrovascular disease. Our results suggest that improving one's BCS could be a valuable intervention to prevent early brain health decline.

Background: Recent hypertension guidelines for the general population have included race-specific recommendations for antihypertensives, whereas current stroke-specific recommendations for antihypertensives do not vary by race. The impact of these guidelines on antihypertensive regimen changes over time, and if this has varied by prevalent stroke status, is unclear., Methods: The use of antihypertensive medications was studied cross-sectionally among self-identified Black and White participants, aged ≥45 years, with and without history of stroke, from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Participants completed an in-home examination in 2003-2007 (visit 1) with/without an examination in 2013-2016 (visit 2). Stratified by prevalent stroke status, logistic regression mixed models examined associations between antihypertensive class use for visit 2 versus visit 1 and Black versus White individuals with an interaction adjusted for demographics, socioeconomic status, and vascular risk factors/vital signs., Results: Of 17 244 stroke-free participants at visit 1, Black participants had greater adjusted odds of angiotensin-converting enzyme inhibitor usage than White participants (odds ratio [OR], 1.51 [95% CI, 1.30-1.77]). This difference was smaller in the 7476 stroke-free participants at visit 2 (OR, 1.16 [95% CI, 1.08-1.25]). In stroke-free participants at visit 1, Black participants had lower odds of calcium channel blocker (CCB) usage than White participants (OR, 0.47 [95% CI, 0.41-0.55]), but CCB usage did not differ significantly between Black and White stroke-free participants at visit 2 (OR, 1.02 [95% CI, 0.95-1.09]). Among 1437 stroke survivor participants at visit 1, Black participants had lower odds of CCB use than White participants (OR, 0.34 [95% CI, 0.26-0.45]). In 689 stroke survivor participants at visit 2, CCB use did not differ between Black and White participants (OR, 0.80 [95% CI, 0.61-1.06])., Conclusions: Racial differences in the use of guideline-recommended antihypertensives decreased between 2003-2007 and 2013-2016 in stroke-free individuals. In stroke survivors, racial differences in CCB usage narrowed over the time periods. These findings suggest there is still a mismatch between race-specific hypertension guidelines and recent clinical practice., Competing Interests: Dr Royan receives salary support as an Assistant Editor at JAMA Network Open. Dr Long receives grant/contract support from the Centers for Disease Control and Prevention, the National Institutes of Health, Patient-Centered Outcomes Research Institute, and Amgen, and reports employment by West Virginia University. Dr Levine receives grant/contract support from the National Institutes of Health and compensation from Northwestern University for consultant services. Dr Gorelick receives consultant support from AbbVie and End Point Review Committee support from Bausch Health US, LLC, ICON Pharma, LabCorp (aka Lab Corporation), Pharmaceutical Research Associates, Sanofi and Genzyme US Companies, Takeda Pharmaceutical Company, and Union Chimique Belge (UCB). The other authors report no conflicts.

Importance: Claims data with International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes are routinely used in clinical research. However, the use of ICD-10 codes to define incident stroke has not been validated against expert-adjudicated outcomes in the US population., Objective: To develop and validate the accuracy of an ICD-10 code list to detect incident stroke events using Medicare inpatient fee-for-service claims data., Design, Setting, and Participants: This cohort study used data from 2 prospective population-based cohort studies, the Atherosclerosis Risk in Communities (ARIC) study and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, and included participants aged 65 years or older without prior stroke who had linked Medicare claims data. Stroke events in the ARIC and REGARDS studies were identified via active surveillance and adjudicated by expert review. Medicare-linked ARIC data (2016-2018) were used to develop a list of ICD-10 codes for incident stroke detection. The list was validated using Medicare-linked REGARDS data (2016-2019). Data were analyzed from September 1, 2022, through September 30, 2023., Exposures: Stroke events detected in Medicare claims vs expert-adjudicated stroke events in the ARIC and REGARDS studies., Main Outcomes and Measures: The main outcomes were sensitivity and specificity of incident stroke detection using ICD-10 codes., Results: In the ARIC study, there were 110 adjudicated incident stroke events among 5194 participants (mean [SD] age, 80.1 [5.3] years) over a median follow-up of 3.0 (range, 0.003-3.0) years. Most ARIC participants were women (3160 [60.8%]); 993 (19.1%) were Black and 4180 (80.5%) were White. Using the primary diagnosis code on a Medicare billing claim, the ICD-10 code list had a sensitivity of 81.8% (95% CI, 73.3%-88.5%) and a specificity of 99.1% (95% CI, 98.8%-99.3%) to detect incident stroke. Using any diagnosis code on a Medicare billing claim, the sensitivity was 94.5% (95% CI, 88.5%-98.0%) and the specificity was 98.4% (95% CI, 98.0%-98.8%). In the REGARDS study, there were 140 adjudicated incident strokes among 6359 participants (mean [SD] age, 75.8 [7.0] years) over a median follow-up of 4.0 (range, 0-4.0) years. More than half of the REGARDS participants were women (3351 [52.7%]); 1774 (27.9%) were Black and 4585 (72.1%) were White. For the primary diagnosis code, the ICD-10 code list had a sensitivity of 70.7% (95% CI, 63.2%-78.3%) and a specificity of 99.1% (95% CI, 98.9%-99.4%). For any diagnosis code, the ICD-10 code list had a sensitivity of 77.9% (95% CI, 71.0%-84.7%) and a specificity of 98.9% (95% CI, 98.6%-99.2%)., Conclusions and Relevance: These findings suggest that ICD-10 codes could be used to identify incident stroke events in Medicare claims with moderate sensitivity and high specificity.

Introduction: It is unclear whether moderate-to-vigorous physical activity (MVPA) is associated with a lower mortality risk, over and above its contribution to total physical activity volume., Methods: 46,682 adults (mean age: 64 years) were included in a meta-analysis of nine prospective cohort studies. Each cohort generated tertiles of accelerometry-measured physical activity volume and volume-adjusted MVPA. Hazard ratios (HR, with 95% confidence intervals) for mortality were estimated separately and in joint models combining volume and MVPA. Data was collected between 2001 and 2019 and analyzed in 2023., Results: During a mean follow-up of 9 years, 4,666 deaths were recorded. Higher physical activity volume, and a greater contribution from volume-adjusted MVPA, were each associated with lower mortality hazard in multivariable-adjusted models. Compared to the least active tertile, higher physical activity volume was associated with a lower mortality (HRs: 0.62; 0.58, 0.67 and 0.50; 0.42, 0.60 for ascending tertiles). Similarly, a greater contribution from MVPA was associated with a lower mortality (HRs: 0.94; 0.85, 1.04 and 0.88; 0.79, 0.98). In joint analysis, a lower mortality from higher volume-adjusted MVPA was only observed for the middle tertile of physical activity volume., Conclusions: The total volume of physical activity was associated with a lower risk of mortality to a greater extent than the contribution of MVPA to physical activity volume. Integrating any intensity of physical activity into daily life may lower mortality risk in middle-aged and older adults, with a small added benefit if the same amount of activity is performed with a higher intensity., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The 21-point Brain Care Score (BCS) is a novel tool designed to motivate individuals and care providers to take action to reduce the risk of stroke and dementia by encouraging lifestyle changes. Given that late-life depression is increasingly recognized to share risk factors with stroke and dementia, and is an important clinical endpoint for brain health, we tested the hypothesis that a higher BCS is associated with a reduced incidence of future depression. Additionally, we examined its association with a brain health composite outcome comprising stroke, dementia, and late-life depression., Methods: The BCS was derived from the United Kingdom Biobank baseline evaluation in participants with complete data on BCS items. Associations of BCS with the risk of subsequent incident late-life depression and the composite brain health outcome were estimated using multivariable Cox proportional hazard models. These models were adjusted for age at baseline and sex assigned at birth., Results: A total of 363,323 participants were included in this analysis, with a median BCS at baseline of 12 (IQR: 11-14). There were 6,628 incident cases of late-life depression during a median follow-up period of 13 years. Each five-point increase in baseline BCS was associated with a 33% lower risk of incident late-life depression (95% CI: 29%-36%) and a 27% lower risk of the incident composite outcome (95% CI: 24%-30%)., Discussion: These data further demonstrate the shared risk factors across depression, dementia, and stroke. The findings suggest that a higher BCS, indicative of healthier lifestyle choices, is significantly associated with a lower incidence of late-life depression and a composite brain health outcome. Additional validation of the BCS is warranted to assess the weighting of its components, its motivational aspects, and its acceptability and adaptability in routine clinical care worldwide., Competing Interests: CA receives sponsored research support from the US National Institutes of Health, the American Heart Association, and Bayer AG, and has consulted for ApoPharma. GF receives sponsored research support from the National Institute of Mental Health Clinical Global Mental Health Research T32 Fellowship, receives royalties or licenses from Johns Hopkins University Press, University of Chicago Press, Belvoir Press, and the American Psychiatric Press, is on a Data Safety Monitoring Board or Advisory Board of Healthy Hearts Healthy Minds DSMB, is a Board of Directors member at the Rosalynn Carter Institute, and has stock or stock options from Revival Therapeutics Consultant. LG-M receives sponsored research support from the American Heart grant number 963719. JR receives sponsored research support from the US National Institutes of Health and the American Heart Association, and receives payments for expert testimony and consulting fees from the National Football League. EM is an employee of Regeneron Genetics Center. The remaining 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.​ The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Singh, Rivier, Papier, Chemali, Gutierrez-Martinez, Parodi, Mayerhofer, Senff, Clocchiatti-Tuozzo, Nunley, Newhouse, Ouyang, Westover, Tanzi, Lazar, Pikula, Ibrahim, Brouwers, Howard, Howard, Yechoor, Littlejohns, Sheth, Rosand, Fricchione, Anderson and Falcone.)

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.

Background: Hypertension is a highly prevalent cardiovascular disease risk factor that may be related to inflammation. Whether adverse levels of specific inflammatory cytokines relate to hypertension is unknown. The present study sought to determine whether higher levels of IL (interleukin)-1β, IL-6, TNF (tumor necrosis factor)-α, IFN (interferon)-γ, IL-17A, and CRP (C-reactive protein) are associated with a greater risk of incident hypertension., Methods: The REGARDS study (Reasons for Geographic and Racial Difference in Stroke) is a prospective cohort study that recruited 30 239 community-dwelling Black and White adults from the contiguous United States in 2003 to 2007 (visit 1), with follow-up 9 years later in 2013 to 2016 (visit 2). We included participants without prevalent hypertension who attended follow-up 9 years later and had available laboratory measures and covariates of interest. Poisson regression estimated the risk ratio of incident hypertension by level of inflammatory biomarkers., Results: Among 1866 included participants (mean [SD] aged of 62 [8] years, 25% Black participants, 55% women), 36% developed hypertension. In fully adjusted models comparing the third to first tertile of each biomarker, there was a greater risk of incident hypertension for higher IL-1β among White (1.24 [95% CI, 1.01-1.53]) but not Black participants (1.01 [95% CI, 0.83-1.23]) and higher TNF-α (1.20 [95% CI, 1.02-1.41]) and IFN-γ (1.22 [95% CI, 1.04-1.42]) among all participants. There was no increased risk with IL-6, IL-17A, or CRP., Conclusions: Higher levels of IL-1β, TNF-α, and IFN-γ, representing distinct inflammatory pathways, are elevated in advance of hypertension development. Whether modifying these cytokines will reduce incident hypertension is unknown., Competing Interests: Disclosures None.

Background: It is unclear how post-stroke cognitive trajectories differ by stroke type and ischemic stroke subtype. We studied associations between stroke types (ischemic, hemorrhagic), ischemic stroke subtypes (cardioembolic, large artery atherosclerotic, lacunar/small vessel, cryptogenic/other determined etiology), and post-stroke cognitive decline., Methods: This pooled cohort analysis from four US cohort studies (1971-2019) identified 1,143 dementia-free individuals with acute stroke during follow-up: 1,061 (92.8%) ischemic, 82 (7.2%) hemorrhagic, 49.9% female, 30.8% Black. Median age at stroke was 74.1 (IQR, 68.6, 79.3) years. Outcomes were change in global cognition (primary) and changes in executive function and memory (secondary). Outcomes were standardized as T-scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Median follow-up for the primary outcome was 6.0 (IQR, 3.2, 9.2) years. Linear mixed-effects models estimated changes in cognition after stroke., Results: On average, the initial post-stroke global cognition score was 50.78 points (95% CI, 49.52, 52.03) in ischemic stroke survivors and did not differ in hemorrhagic stroke survivors (difference, -0.17 points [95% CI, -1.64, 1.30]; P =0.82) after adjusting for demographics and pre-stroke cognition. On average, ischemic stroke survivors showed declines in global cognition, executive function, and memory. Post-stroke declines in global cognition, executive function, and memory did not differ between hemorrhagic and ischemic stroke survivors. 955 ischemic strokes had subtypes: 200 (20.9%) cardioembolic, 77 (8.1%) large artery atherosclerotic, 207 (21.7%) lacunar/small vessel, 471 (49.3%) cryptogenic/other determined etiology. On average, small vessel stroke survivors showed declines in global cognition and memory, but not executive function. Initial post-stroke cognitive scores and cognitive declines did not differ between small vessel survivors and survivors of other ischemic stroke subtypes. Post-stroke vascular risk factor levels did not attenuate associations., Conclusion: Stroke survivors had cognitive decline in multiple domains. Declines did not differ by stroke type or ischemic stroke subtype.

Background and Objectives: Improving access to health care providers with clinical expertise in stroke care may influence the use of recommended strategies for reducing disparities in quality of care. Few studies have examined differences in the receipt of evaluation by neurologists during the hospital stay. We examined the proportion of individuals hospitalized for acute ischemic stroke who received evaluation by a neurologist during the hospital stay and characterized differences in receipt of neurologist evaluation by race (Black vs White), sex, age, and study region (Stroke Belt residence vs other) among those experiencing a stroke who were participating in a national cohort study., Methods: This cross-sectional study was conducted using medical record data abstracted from 1,042 participants enrolled in the national Reasons for Geographic and Racial Differences in Stroke cohort study (2003-2007) who experienced an adjudicated ischemic stroke between 2003 and 2016. Participants with a history of stroke before baseline, in-hospital death, hospice discharge following their stroke, or incomplete records were excluded resulting in 839 cases. Differences were assessed using modified Poisson regression adjusting for participant-level and hospital-level factors., Results: Of the 839 incident strokes, 722 (86%) received evaluation by a neurologist during the hospital stay. There were no significant differences by age, race, or sex, yet Stroke Belt residents and those receiving care in rural hospitals were significantly less likely to receive neurologist evaluation compared with non-Stroke Belt residents (relative risk [RR] 0.95; 95% CI 0.90-1.01) and participants receiving care in urban hospitals (RR 0.74; 95% CI 0.63-0.86). Participants with a greater level of poststroke functional impairment (modified Rankin scale) and those with a greater number of risk factors were more likely to receive neurologist evaluation compared with those with lower levels of poststroke functional impairment (RR 1.04; 95% CI 1.01-1.06) and fewer risk factors (RR 1.02; 95% CI 1.00-1.04)., Discussion: While differences in access to neurologists during the hospital stay were partially explained by patient need in our study, there were also significant differences in access by region and urban-rural hospital status. Ensuring access to neurologists during the hospital stay in such settings may require policy-level and/or system-level changes.

Background: Post stroke sleep duration could increase the risk of death. This study tested the hypothesis that inadequate sleep duration is associated with increased mortality among stroke survivors., Methods: The REasons for Geographic And Racial Differences in Stroke (REGARDS), a national population-based longitudinal study, was the data source. Sleep duration was ascertained between 2013 and 2016 among stroke survivors who were subsequently followed up until death or censored on December 31, 2022. Sleep duration was estimated as the difference between wake-up time and bedtime to which was subtracted the time spent in bed without sleep. Cox proportional hazards regression models were employed to investigate the association between sleep duration and all-cause mortality adjusting for demographic factors, socioeconomic factors, behavioral factors, and co-morbidities., Results: A total of 468 non-Hispanic Black and White stroke survivors were included in this analysis. The mean age was 76.3 years, 52.6% were females and 56.0% were non-Hispanic White individuals. The distribution of short (≤6 h), adequate (7.0-8.9 h), and long sleep (≥9 h) was 30.3%, 44.7%, and 25%, respectively. Over a mean follow-up of 5.0 years, 190 (40.6%) deaths occurred. Compared to stroke survivors with adequate sleep (7.0-8.9 h), stroke survivors with long sleep (≥9 h) were at increased risk of all-cause mortality (HR=1.46, 95% CI=1.01, 2.12). However, short sleep (≤6 h) was not significantly associated with an increased risk of all-cause mortality (HR=1.31, 95% CI=0.90, 1.91). Subgroup analyses indicated higher risk in the age <75 years, females, non-Hispanic Black individuals, and those living in the Stroke Belt region, but those differences were not statistically significant., Conclusion: In this study of stroke survivors, 9 hours or more of sleep per day was associated with an increased risk of all-cause mortality. This finding suggests that excessive sleep duration may be a warning sign of poor life expectancy in stroke survivors., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Background and Objectives: Racial/ethnic differences have been documented in the relationship between obstructive sleep apnea (OSA) and stroke incidence, yet racial differences in OSA symptoms or treatment and their relationship with stroke incidence are underexplored and may contribute to stroke disparities. We comprehensively examined OSA symptoms and their relationships to stroke incidence by race/ethnicity., Methods: Data were collected from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a population-based cohort of Black and White individuals in the United States. Participants free from a stroke diagnosis at baseline were included. Participants self-reported the following: (1) snoring; (2) daytime sleepiness; (3) provider-diagnosed sleep apnea (PDSA); and (4) treatment for PDSA using positive airway pressure (PAP). OSA risk was categorized as high or low based on the Berlin Sleep Questionnaire. Incident stroke was defined as first occurrence of stroke over an average of 12 (SD 3.9) years of follow-up. We report the relationships between snoring, OSA risk, PDSA, PAP therapy use, and incident stroke by race/ethnicity using Cox proportional hazards models after adjusting for demographic and socioeconomic factors and stroke risk factors., Results: Among the 22,192 participants (mean age [SD] 64.2[9.1] years), 38.1% identified as Black. Overall, snoring was not associated with incident stroke (hazard ratio [HR] 0.98, 95% CI 0.85-1.13). However, among White individuals but not Black individuals, high OSA risk and PDSA were associated with incident stroke (HR 1.22, 95% CI 1.01-1.47; HR 1.33, 95% CI 1.04-1.70, respectively). PAP therapy use among those with PDSA (compared with non-PDSA) was associated with incident stroke in White individuals (HR 1.38, 95% CI 1.05-1.80). PAP therapy use among those with PDSA (compared with those with PDSA without PAP therapy use) was associated with reduced risk of incident stroke in Black (HR 0.39, 95% CI 0.17-0.91) but not White (HR 0.63, 95% CI 0.37-1.10) individuals., Discussion: White individuals with high OSA risk and those with PDSA with or without PAP therapy use were at increased incident stroke risk, whereas Black individuals reporting PDSA and PAP had reduced incident stroke risk relative to those not using PAP. Future research is needed to understand the mechanisms underlying racial differences in OSA and stroke such as differences in assessment modes and treatment.

Background: Life's Simple 7 (LS7) is an easily calculated and interpreted metric of cardiovascular health based on 7 domains: smoking, diet, physical activity, body mass index, blood pressure, cholesterol, and fasting glucose. The Life's Essential 8 (LE8) metric was subsequently introduced, adding sleep metrics and revisions of the previous 7 domains. Although calculating LE8 requires additional information, we hypothesized that it would be a more reliable index of cardiovascular health., Methods: Both the LS7 and LE8 metrics yield scores with higher values indicating lower risk. These were calculated among 11 609 Black and White participants free of baseline cardiovascular disease (CVD) in the Reasons for Geographic and Racial Differences in Stroke study, enrolled in 2003 to 2007, and followed for a median of 13 years. Differences in 10-year risk of incident CVD (coronary heart disease or stroke) were calculated as a function LS7, and LE8 scores were calculated using Kaplan-Meier and proportional hazards analyses. Differences in incident CVD discrimination were quantified by difference in the c-statistic., Results: For both LS7 and LE8, the 10-year risk was approximately 5% for participants around the 99th percentile of scores, and a 4× higher 20% risk for participants around the first percentile. Comparing LS7 to LE8, 10-year risk was nearly identical for individuals at the same relative position in score distribution. For example, the "cluster" of 2013 participants with an LS7 score of 7 was at the 35.8th percentile in distribution of LS7 scores, and had an estimated 10-year CVD risk of 8.4% (95% CI, 7.2%-9.8%). In a similar location in the LE8 distribution, the 1457 participants with an LE8 score of 60±2.5 at the 39.4th percentile of LE8 scores had a 10-year risk of CVD of 8.5% (95% CI, 7.1%-10.1%), similar to the cluster defined by LS7. The age-race-sex adjusted c-statistic of the LS7 model was 0.691 (95% CI, 0.667-0.705), and 0.695 for LE8 (95% CI, 0.681-0.709) ( P for difference, 0.12)., Conclusions: Both LS7 and LE8 were associated with incident CVD, with discrimination of the 2 indices practically indistinguishable. As a simpler metric, LS7 may be favored for use by the general population and clinicians., Competing Interests: None.

Objectives: Adiposity may have a role in the risk of dementia. Fewer studies have focused on the relationship between change in adiposity and cognitive decline. Our study aimed to explore the association between the change in adiposity and cognitive function in Black and White older adults., Methods: The participants were 12,204 older adults without cognitive impairment (62.8 ± 8.0 years) in the United States. The percent body mass index change (%BMI change) and percent waist circumference change (%WC change) were measured at 2 in-home visits (first: 2003-2007, second: 2013-2016). Cognitive status was assessed by the Six-Item Screener annually. Memory and executive function were measured by word list learning, MOCA recall and orientation, and letter and animal fluency every 2 years. Logistic regression or linear regression models were used to estimate the relationship between percent change in adiposity and cognitive function., Results: After 12.7 ± 1.7 years, a greater decrease in %BMI change or %WC change was significantly associated with a higher risk of cognitive impairment. Compared to older adults with -5% ≤ change ≤ 5% from baseline, a significantly higher risk of cognitive impairment and greater loss in memory and executive function were found among those who experienced more than a 10% decline in %BMI change or %WC change. Older adults who experienced a 5%-10% decrease in %BMI change had a higher risk of cognitive impairment and greater loss of memory compared to those with -5% ≤ change ≤ 5%., Discussion: A greater decrease in %BMI (>5%) and %WC (>10%) change was associated with greater cognitive loss observed over time., (© The Author(s) 2023. 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.)

This study investigates correlates of anti-S1 antibody response following COVID-19 vaccination in a U.S. population-based meta-cohort of adults participating in longstanding NIH-funded cohort studies. Anti-S1 antibodies were measured from dried blood spots collected between February 2021-August 2022 using Luminex-based microsphere immunoassays. Of 6245 participants, mean age was 73 years (range, 21-100), 58% were female, and 76% were non-Hispanic White. Nearly 52% of participants received the BNT162b2 vaccine and 48% received the mRNA-1273 vaccine. Lower anti-S1 antibody levels are associated with age of 65 years or older, male sex, higher body mass index, smoking, diabetes, COPD and receipt of BNT16b2 vaccine (vs mRNA-1273). Participants with a prior infection, particularly those with a history of hospitalized illness, have higher anti-S1 antibody levels. These results suggest that adults with certain socio-demographic and clinical characteristics may have less robust antibody responses to COVID-19 vaccination and could be prioritized for more frequent re-vaccination., (© 2024. The Author(s).)

Background: Life-space mobility, which measures the distance, frequency, and independence achieved as individuals move through their community, is one of the most important contributors to healthy aging. The University of Alabama at Birmingham Life-Space Assessment (LSA) is the most commonly used measure of life-space mobility in older adults, yet U.S. national norms for LSA have not previously been reported. This study reports such norms based on age and sex among community-dwelling older adults., Methods: A cross-sectional analysis using data from the national REasons for Geographic and Racial Disparities in Stroke cohort study. LSA data were available for 10 118 Black and White participants over age 50, which were grouped by age (in 5-year increments) and sex, weighted for the U.S. national population. Correlations were calculated between LSA and measures of functional and cognitive impairment and physical performance., Results: The weighted mean LSA ranged from 102.9 for 50-54-year-old males to 69.5 for males aged 85 and older, and from 102.1 for 50-54-year-old females to 60.1 for females aged 85 and older. LSA was strongly correlated with measures of timed walking, activities of daily living, cognition, depressive symptoms, and quality of life (all p < .001)., Conclusions: We report U.S. national norms for LSA among community-dwelling Black and White older adults. These norms can serve as a reference tool for determining if clinical and research samples have greater or lesser life-space mobility than typical older adults in the United States for their age and sex., (© The Author(s) 2023. 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.)

Objective: A health disparity is a health difference that adversely affects disadvantaged populations, and thus could plausibly be due to social factors. Biopsychosocial processes that contribute to health disparities are not well-understood. Establishing whether candidate biomarkers are similarly associated with biologically relevant psychosocial constructs across health disparity groups is a current gap in our understanding., Method: This study examined associations between perceived stress, depressive symptoms, and social support with C-reactive protein (CRP) and whether associations varied by race, sex, or income in 24,395 Black and White adults aged 45 years or older from the REGARDS population-based national cohort., Results: The association between depressive symptoms and CRP was slightly larger at higher (vs. lower) income levels and larger for men (vs. women) but did not vary by race. Associations between stress and CRP and social support and CRP were not moderated by income, race, or sex. An interaction between race and income, evidenced that higher income was more strongly associated with lower CRP in White participants compared to Black participants, consistent with the idea of "diminishing returns" of income for the health of Black Americans., Conclusions: Basic associations between these psychosocial factors and CRP are small and generally similar across income, race, and sex. Black and lower-income Americans likely evidence higher CRP due to greater exposure to psychosocial risk factors rather than increased biological vulnerability to these exposures. Additionally, given small associations, CRP should not be used as a proxy for the construct of psychosocial stress. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: We sought to determine if risk for obstructive sleep apnea (OSA), a history of OSA, and/or treatment of OSA has a different association with incident cognitive impairment or cognitive decline in Black individuals and White individuals., Methods: To determine whether the risk for OSA, a history of OSA, and/or treatment of OSA has a different association with incident cognitive impairment or cognitive decline in Black individuals and White individuals; data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) was used. Participants that completed the sleep questionnaire module, had baseline cognitive assessment, and at least one cognitive assessment during follow-up were included. Risk of OSA was determined based on Berlin Sleep Questionnaire. History of sleep apnea was determined based on structured interview questions. Optimally treated OSA was defined as treated sleep apnea as at least 4 h of continuous positive airway pressure use per night for ≥5 nights per week., Results: In 19,017 participants stratified by race, White participants with history of OSA were 1.62 times more likely to have incident cognitive impairment compared to White participants without history of OSA after adjusting for demographic characteristics, history, and lifestyle factors (OR = 1.62, 95% CI = 1.05-2.50, p-value = 0.03). This relationship was not seen in Black participants (OR = 0.92, 95% CI = 0.60-1.43, p-value = 0.72)., Discussion: A previous diagnosis of OSA is associated with incident cognitive impairment in White Americans but not Black Americans. Further investigations are required to determine the mechanism for this difference., 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 © 2023 Elsevier B.V. All rights reserved.)

Objectives: Work schedule demands contribute to circadian disruption and may influence health via an inflammatory response. We examined the impact of shiftwork and long work hours on inflammation in a national US sample., Methods: Participants included 12 487 employed black and white men and women aged ≥45 years enrolled in the REasons for Geographic and Racial Differences in Stroke Study who completed an occupational questionnaire (2011-2013) and clinical examination (2013-2016). Cross-sectional associations between shiftwork and work hours with log-transformed high-sensitivity C reactive protein (CRP) and white blood cell (WBC) count were examined by multiple linear regression analysis, overall and by race-sex subgroups., Results: Overall, rotating shift workers had higher log-CRP concentration compared with day workers (β=0.09, 95% CI:0.02 to 0.16) and findings for WBC were null. Black women had the highest geometric mean CRP (2.82 mg/L), while white men had the highest WBC (6.35×10 9 /L). White men who worked afternoons had higher log-CRP compared with those who worked days (β=0.20, 95% CI: 0.08 to 0.33). Black men engaged in shiftwork <10 years working ≥55 hours/week had higher log-CRP and log-WBC compared with those working days <55 hours/week (β=0.33, 95% CI: 0.02 to 0.64 and β=0.10, 95% CI: 0.003 to 0.19). Among shift workers, non-retired white women working forward and backward shift rotations had higher log-CRP compared with those working forward only (β=0.49, 95% CI: 0.02 to 0.96)., Conclusions: Shift workers had higher inflammatory markers compared with day workers and race-sex disparities should be examined further. These findings highlight a potential biological pathway linking work schedule demands and chronic disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The association of hypertension (HTN) severity and control with the risk of incident atrial fibrillation (AF) is unclear., Hypothesis: Increased HTN severity and poorer blood pressure control would be associated with an increased risk of incident AF., Methods: This analysis included 9485 participants (mean age 63 ± 8 years; 56% women; 35% Black). Participants were stratified into six mutually exclusive groups at baseline-normotension (n = 1629), prehypertension (n = 704), controlled HTN (n = 2224), uncontrolled HTN (n = 4123), controlled apparent treatment-resistant hypertension (aTRH) (n = 88), and uncontrolled aTRH (n = 717). Incident AF was ascertained at the follow-up visit, defined by either electrocardiogram or self-reported medical history of a physician diagnosis. Multivariable logistic regression analyses adjusted for demographic and clinical variables., Results: Over an average of 9.3 years later, 868 incident AF cases were detected. Compared to those with normotension, incident AF risk was highest for those with aTRH (controlled aTRH: odds ratio (OR) 2.95; 95% confidence interval (CI) 1.60, 5.43, & uncontrolled aTRH: OR 2.47; 95% CI 1.76, 3.48). The increase in AF risk was smaller for those on no more than three antihypertensive agents regardless of their blood pressure control (controlled OR 1.72; 95% CI 1.30, 2.29 and uncontrolled OR 1.56; 95% CI 1.14, 2.13)., Conclusions: The risk of developing AF is increased in all individuals with HTN. Risk is highest in those aTRH regardless of blood pressure control. A more aggressive approach that focuses on lifestyle and pharmacologic measures to either prevent HTN or better control HTN during earlier stages may be particularly beneficial in reducing related AF risk., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Low educational attainment is associated with excess cancer mortality. However, the mechanisms driving this association remain unknown., Methods: Using data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, we evaluated the associations of participant and parental/caregiver education with cancer mortality using Cox proportional hazards models, adjusting for socio-demographic characteristics and health conditions. We used principal components analysis to generate indices of measures representing the social determinants of health (SDOH) and health behaviors. We used structural equation modeling to determine if the association between educational attainment and cancer mortality was mediated by these domains., Results: Among 30,177 REGARDS participants included in this analysis, 3798 (12.6%) had less than a high school degree. In fully adjusted models, those without a high school education experienced about 50% greater risk of death than high school graduates and higher (White participants HR: 1.47; 95% CI: 1.23, 1.76 and Black HR: 1.54; 95% CI: 1.33, 1.79). There was evidence of a modest mediation effect for the association between education and cancer mortality by the SDOH domain score (White total effect HR: 1.25; 95% CI: 1.18, 1.33, indirect effect HR: 1.04; 95% CI: 1.03, 1.05, direct effect HR: 1.21; 95% CI: 1.14, 1.28 and Black total effect HR: 1.24; 95% CI: 1.18, 1.29, indirect effect HR: 1.04; 95% CI: 1.03, 1.05, direct effect HR: 1.19; 95% CI: 1.14, 1.24). There was no evidence of mediation by the health behaviors score. No significant associations were found for female caregiver/mother's or male caregiver/father's education (N = 13,209)., Conclusions: In conclusion, participant education was strongly associated with cancer mortality, and this association was partially mediated by the SDOH domain score., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Wilson reports research funding paid to Duke University from AstraZeneca, outside the submitted work. All other authors declare no competing interests., (© 2023 The Authors.)

The American South has been characterized as a Stroke Belt due to high cardiovascular mortality. We examine whether mortality rates and race differences in rates reflect birthplace exposure to Jim Crow-era inequalities associated with the Plantation South. The plantation mode of agricultural production was widespread through the 1950s when older adults of today, if exposed, were children. We use proportional hazards models to estimate all-cause mortality in Non-Hispanic Black and White birth cohorts (1920-1954) in a sample (N = 21,941) drawn from REasons for Geographic and Racial Differences in Stroke (REGARDS), a national study designed to investigate Stroke Belt risk. We link REGARDS data to two U.S. Plantation Censuses (1916, 1948) to develop county-level measures that capture the geographic overlap between the Stroke Belt, two subregions of the Plantation South, and a non-Plantation South subregion. Additionally, we examine the life course timing of geographic exposure: at birth, adulthood (survey enrollment baseline), neither, or both portions of life. We find mortality hazard rates higher for Black compared to White participants, regardless of birthplace, and for the southern-born compared to those not southern-born, regardless of race. Race-specific models adjusting for adult Stroke Belt residence find birthplace-mortality associations fully attenuated among White-except in one of two Plantation South subregions-but not among Black participants. Mortality hazard rates are highest among Black and White participants born in this one Plantation South subregion. The Black-White mortality differential is largest in this birthplace subregion as well. In this subregion, the legacy of pre-Civil War plantation production under enslavement was followed by high-productivity plantation farming under the southern Sharecropping System., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background Non-Hispanic Black adults have a higher proportion of vascular cognitive impairment and Alzheimer's disease and related dementias compared with non-Hispanic White adults that may be due to differences in the burden of cerebral small vessel disease and risk alleles for Alzheimer's disease and related dementias. We describe here the methods of an ancillary study to the REGARDS (Reason for Geographic and and Racial Difference in Stroke) study, which will examine the role of magnetic resonance imaging markers of cerebral small vessel disease and vascular as well as genetic risk factors for Alzheimer's disease and related dementias in racial disparity in the prevalence and trajectory of vascular cognitive impairment and dementia in non-Hispanic White and non-Hispanic Black participants. Methods In participants with no prior history of stroke who had an incident stroke or transient ischemic attack after enrollment in the study, magnetic resonance imaging scans will be evaluated using the Standards for Reporting Vascular Changes on Neuroimaging international consensus criteria and automated analysis pipelines for quantification of cerebral small vessel disease. Participants will be genotyped for APOE ε4 and TREM2 risk alleles for Alzheimer's disease and related dementias. The 6-item screener will define global cognitive function and be the primary cognitive outcome. Conclusions With at least 426 non-Hispanic Black and 463 non-Hispanic White participants who have at least 2 prior and 2 poststroke or transient ischemic attack cognitive assessments, we will have at least 80% power to detect a minimum effect size of 0.09 SD change in Z score, with correction for as many as 20 tests (ie, at P <0.0025, after adjusting for up to 20 covariates) for cognitive decline.

Background: We examined whether the risk of incident atrial fibrillation (AF) in a large, biracial, prospective cohort is lower in participants who adhere to heart-healthy dietary patterns and higher in participants who adhere to less heart-healthy diets., Methods: Between 2003 and 2007, the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study enrolled 30,239 Black and White Americans aged 45 years or older. Dietary patterns (convenience, plant-based, sweets, Southern, and alcohol and salads) and the Mediterranean diet score (MDS) were derived based on food frequency questionnaire data. The primary outcome was incident AF at the follow-up visit 2013-2016, defined by either electrocardiogram or self-reported medical history of a physician diagnosis., Results: This study included 8977 participants (mean age 63 ± 8.3 years; 56% women; 30% Black) free of AF at baseline who completed the follow-up exam an average of 9.4 years later. A total of 782 incident AF cases were detected. In multivariable logistic regression analyses, neither the MDS score (odds ratio (OR) per SD increment = 1.03; 95% confidence interval (CI) 0.95-1.11) or the plant-based dietary pattern (OR per SD increment = 1.03; 95% CI 0.94-1.12) were associated with AF risk. Additionally, an increased AF risk was not associated with any of the less-healthy dietary patterns., Conclusions: While specific dietary patterns have been associated with AF risk factors, our findings fail to show an association between diet patterns and AF development., (© 2023. The Author(s).)

Background: Retirement represents a crucial transitional period for many adults with possible consequences for cognitive aging. We examined trajectories of cognitive change before and after retirement in Black and White adults., Methods: Longitudinal examination of up to 10 years (mean = 7.1 ± 2.2 years) using data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study-a national, longitudinal study of Black and White adults ≥45 years of age. Data were from 2226 members of the REGARDS study who retired around the time when an occupational ancillary survey was administered. Cognitive function was an average of z-scores for tests of verbal fluency, memory, and global function., Results: Cognitive functioning was stable before retirement (Estimate = 0.05, p = 0.322), followed by a significant decline after retirement (Estimate = -0.15, p < 0.001). The decline was particularly pronounced in White (Estimate = -0.19, p < 0.001) compared with Black (Estimate = -0.07, p = 0.077) participants, twice as large in men (Estimate = -0.20, p < 0.001) compared with women (Estimate = -0.11, p < 0.001), highest among White men (Estimate = -0.22, p < 0.001) and lowest in Black women (Estimate = -0.04, p = 0.457). Greater post-retirement cognitive decline was also observed among participants who attended college (Estimate = -0.14, p = 0.016). While greater work complexity (Estimate = 0.92, p < 0.05) and higher income (Estimate = 1.03, p < 0.05) were related to better cognitive function at retirement, neither was significantly related to cognitive change after retirement., Conclusion: Cognitive functioning may decline at an accelerated rate immediately post-retirement, more so in White adults and men than Black adults and women. Lifelong structural inequalities including occupational segregation and other social determinants of cognitive health may obscure the role of retirement in cognitive aging., (© 2023 The American Geriatrics Society.)

The national mandate to improve health equity in the United Sates is advancing. Racial and ethnic disparities in various aspects of health care have been clearly delineated, and sources of such disparities have been identified. However, implementing solution-focused interventions to eradicate such disparities, thereby achieving health equity in all US communities, has remained a daunting challenge, and no area more so, than with neurologic diseases. To assure success with bridging prominent disparities in neurologic outcomes, the pipeline of neurologic disparities researchers needs to be broadened, numbers of mid-career and senior disparities scientists sustained, partnerships with community stakeholders enhanced, incentivization of academic organizations pursued, education of all neurologic researchers conducted, and exemplary training of funding agency staff prioritized. To improve the current state of neurologic disparities, the National Institute of Neurological Disorders and Stroke assembled a working group of its advisory council. (2020-2022) to examine the state of health disparity training and research. Through consensus building, we present identified gaps and recommendations to the current state of underrepresented groups in medicine in health disparity research and its training and curricula in the United States., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Purpose: To measure the association of baseline psychological symptoms (depressive symptoms and perceived stress) with withdrawal from a cohort study., Methods: Depressive symptoms and perceived stress were obtained using validated measures during the baseline computer-assisted telephonic interview for the REasons for Geographic and Racial Differences in Stroke study a national longitudinal cohort (≥45 years, 42% Black, 55% women) recruited between 2003 and 2007. Participants who completed follow-up after September 1, 2019, were considered active. Primary outcome was time to study withdrawal. The association of psychological symptoms and time-to-withdrawal was measured using Cox proportional hazard regression models with incremental adjustments by demographic and clinical factors., Results: Out of 29,964 participants included in the analysis, 11,111 (37.1%) participants withdrew over the follow-up period (median: 11 years). Compared to participants with low depressive symptoms, those with moderate symptoms had 5% higher risk (aHR= 1.05; 95% CI= 1.00-1.10) and those with high level of depressive had 19% higher risk (aHR= 1.19; 95% CI= 1.11-1.27) of withdrawal in fully adjusted models. No significant association between perceived stress and withdrawal risk was observed., Conclusions: Depressive symptoms were significantly associated with withdrawal. Prevalence of depressive symptoms at baseline is an important indicator of participant retention in large prospective cohorts., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships that may be considered potential competing interests: Chen Lin reports financial support was provided by the Veterans Affairs Medical Center., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The study objective was to investigate the effects of childhood residential mobility on older adult physical and mental health. In REasons for Geographic and Racial Differences in Stroke (REGARDS) Study, we used linear regression models to investigate if number of moves during childhood predicted mental and physical health (SF-12 MCS, PCS), adjusting for demographic covariates, childhood socioeconomic status (SES), childhood social support, and adverse childhood experiences (ACEs). We investigated interaction by age, race, childhood SES, and ACEs. People who moved more during childhood had poorer MCS scores, β = -0.10, SE = 0.05, p = 0.03, and poorer PCS scores, β = -0.25, SE = 0.06, p < 0.0001. Effects of moves on PCS were worse for Black people compared to White people ( p = 0.06), those with low childhood SES compared to high childhood SES ( p = 0.02), and high ACEs compared to low ACEs ( p = 0.01). As family instability accompanying residential mobility, family poverty, and adversity disproportionately affect health, Black people may be especially disadvantaged.

Background Cardiovascular disease is a risk factor for cognitive impairment. Evidence links both lower and higher concentration of the circulating opioid pro-enkephalin A (PENK-A) with stroke risk. We studied the association of plasma PENK-A with incident cognitive impairment. Methods and Results REGARDS (Reasons for Geographic and Racial Differences in Stroke) is a prospective cohort study of 30 239 adults enrolled from 2003 to 2007. Baseline PENK-A was measured in a nested case-control study of 462 participants who developed cognitive impairment over 4.7 years, and 556 controls. Logistic regression and spline plots adjusted for confounders estimated odds ratios (ORs) of cognitive impairment by baseline PENK-A. Interaction terms tested for differences in associations by age, sex, and race. Baseline PENK-A was comparable between cases and controls. There were significant differences in the association of PENK-A with cognitive impairment by sex and age (adjusted P =0.003 and 0.06, respectively). In women but not men, spline plots showed that higher and lower PENK-A were associated with decreased odds of cognitive impairment (ORs for 10th and 90th percentiles versus median, 0.65 [95% CI, 0.43-0.96] and 0.64 [95% CI, 0.41-0.99]), with no difference by age. In men ≥65 years of age but not younger men, higher PENK-A was associated with decreased odds for cognitive impairment (OR for fourth versus first quartile 0.47 [95% CI, 0.22-0.99]); this pattern was not confirmed with spline plotting. Conclusions High and low levels of circulating opioid PENK-A were associated with decreased odds of future cognitive impairment in specific subgroups. Additional research is warranted to understand the biology underlying this association and the observed differences by sex.

Multiple challenges confront procedural trials, including slow enrollment, lack of equipoise among patients and physicians, and failure to achieve adequate masking. Nonetheless, randomized clinical trials provide the best evidence of efficacy. The evolution of technology, techniques, and standards of care during the conduct of procedural trials challenges external validity. In this study, we review how a multicenter trial of revascularization of asymptomatic carotid arteries for stroke prevention has managed changes in treating carotid stenosis and medical management of atherothrombotic disease. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov number: NCT02089217., (Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Importance: Incident stroke is associated with accelerated cognitive decline. Whether poststroke vascular risk factor levels are associated with faster cognitive decline is uncertain., Objective: To evaluate associations of poststroke systolic blood pressure (SBP), glucose, and low-density lipoprotein (LDL) cholesterol levels with cognitive decline., Design, Setting, and Participants: Individual participant data meta-analysis of 4 US cohort studies (conducted 1971-2019). Linear mixed-effects models estimated changes in cognition after incident stroke. Median (IQR) follow-up was 4.7 (2.6-7.9) years. Analysis began August 2021 and was completed March 2023., Exposures: Time-dependent cumulative mean poststroke SBP, glucose, and LDL cholesterol levels., Main Outcomes and Measures: The primary outcome was change in global cognition. Secondary outcomes were change in executive function and memory. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition., Results: A total of 1120 eligible dementia-free individuals with incident stroke were identified; 982 (87.7%) had available covariate data and 138 (12.3%) were excluded for missing covariate data. Of the 982, 480 (48.9%) were female individuals, and 289 (29.4%) were Black individuals. The median age at incident stroke was 74.6 (IQR, 69.1-79.8; range, 44.1-96.4) years. Cumulative mean poststroke SBP and LDL cholesterol levels were not associated with any cognitive outcome. However, after accounting for cumulative mean poststroke SBP and LDL cholesterol levels, higher cumulative mean poststroke glucose level was associated with faster decline in global cognition (-0.04 points/y faster per each 10-mg/dL increase [95% CI, -0.08 to -0.001 points/y]; P = .046) but not executive function or memory. After restricting to 798 participants with apolipoprotein E4 (APOE4) data and controlling for APOE4 and APOE4 × time, higher cumulative mean poststroke glucose level was associated with a faster decline in global cognition in models without and with adjustment for cumulative mean poststroke SBP and LDL cholesterol levels (-0.05 points/y faster per 10-mg/dL increase [95% CI, -0.09 to -0.01 points/y]; P = .01; -0.07 points/y faster per 10-mg/dL increase [95% CI, -0.11 to -0.03 points/y]; P = .002) but not executive function or memory declines., Conclusions and Relevance: In this cohort study, higher poststroke glucose levels were associated with faster global cognitive decline. We found no evidence that poststroke LDL cholesterol and SBP levels were associated with cognitive decline.

The recently published SPACE-2 trial (Stent-Supported Percutaneous Angioplasty of the Carotid Artery Versus Endarterectomy-2) compared 3 treatments to prevent stroke in patients with asymptomatic carotid stenosis ≥70%: (1) carotid endarterectomy plus best medical treatment (BMT), (2) transfemoral carotid artery stenting plus BMT, or (3) BMT alone. Because of low enrollment, the findings of similar safety and efficacy for carotid endarterectomy, carotid artery stenting, or BMT alone were inconclusive. Publication of the CREST (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial)-2 results should provide level A evidence that has been lacking for 2 to 3 decades, to guide treatment of asymptomatic patients with severe carotid stenosis. For symptomatic patients with ≥70% stenosis, no trials are underway to update the degree of benefit reported for carotid endarterectomy by NASCET (North American Carotid Endarterectomy Trial) and ECST (European Carotid Surgery Trial), published in 1991. Subsequently, the use of cigarettes has plummeted, and major improvements in medical treatments and in carotid revascularization have emerged. These advances have coincided with abrupt decline in the clinical end points necessary for treatment comparisons in procedural trials. One of the advances in the invasive management of carotid disease has been transcarotid artery revascularization, already with limited approval by the US Food and Drug Administration. Establishing safety and efficacy of transcarotid artery revascularization compared with carotid endarterectomy, carotid artery stenting, or BMT alone may be challenging because of enrollment, regulatory, and funding barriers to design and complete an adequately powered randomized trial.

Background and Objectives: Reports assessing the association of stroke risk factors with incident stroke have generally assumed a uniform magnitude of associations across the age spectrum, an assumption we assess in this report., Methods: Participants enrolled 2003-2007 in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study who were stroke free at baseline were followed for incident stroke. Associations of traditional stroke risk factors with incident stroke were assessed using (1) proportional hazards analysis based on the baseline age of the participant and (2) Poisson regression analysis assessing associations based on the changing age of the participant during their follow-up (age at exposure). In each analysis, age strata were selected to have a similar number of strokes in each stratum, specifically 45-64, 65-73, and 74+ years for the proportional hazards analysis and 45-69, 70-79, and 80+ years for Poisson regression., Results: A total of 1,405 ischemic stroke events occurred among 28,235 participants over a median follow-up of 11.3 years, with a total of 276,074 person-years exposure. For both analytic approaches, the magnitude of the association with stroke was significantly less at older ages for diabetes (hazard or relative risk decreasing from ≈2.0 in younger strata to ≈1.3 in older strata), heart disease (from ≈2.0 to ≈1.3), and hypertension defined at a threshold of 140/90 mm Hg (from ≈1.80 to ≈1.50); however, there was no age-related difference in the magnitude of the association for smoking, atrial fibrillation, or left ventricular hypertrophy., Discussion: Hypertension and diabetes are 2 of the more important risk factors for stroke; however, their association with stroke risk appears substantially less at older ages. That the magnitude of the association for smoking, atrial fibrillation, and left ventricular hypertrophy does not decrease with age suggests their relative importance in determining stroke risk likely increases with age., (© 2023 American Academy of Neurology.)

Background: The work environment can contribute to the risk of cardiovascular diseases (CVD) including stroke. Our objective was to identify occupations with elevated risk of stroke within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort., Methods: We analyzed incident stroke outcomes (ischemic and hemorrhagic strokes) from 2003 to 2020 and employment characteristics of 13,659 adults aged ≥45 years enrolled in a national population-based cohort study. Using a modified Poisson regression approach, we estimated the relative risks (RRs) and the associated 95% confidence intervals (CI) of stroke in relation to years of employment within each occupation coded using the US Census two-digit Standard Occupation Code. Models were adjusted for Framingham Stroke Risk Score, region, race, age, and body mass index. We conducted stratified analysis by sex, employment time period (pre-1975 vs. post-1975), and region., Results: Workers in the following occupations had a greater risk of stroke with longer duration of employment (per decade): protective service (RR: 2.35, 95% CI: 1.11, 4.97), food preparation and service (RR: 1.51, 95% CI: 1.05, 2.19), and transportation and material moving (RR: 1.30, 95% CI: 1.00, 1.69). The stroke risk in these occupations was disproportionately elevated in men, and differed by region and employment time period., Conclusions: Longer employment in protective service, food preparation and serving, and transportation and materials moving occupations may increase the risk of stroke. Surveillance may uncover specific work-related risk factors in these occupations, leading to interventions to reduce the burden of stroke among US workers., (© 2022 Wiley Periodicals LLC.)

Objectives: Higher inflammation has been linked to poor physical and mental health outcomes, and mortality, but few studies have rigorously examined whether changes in perceived stress and depressive symptoms are associated with increased inflammation within family caregivers and non-caregivers in a longitudinal design., Design: Longitudinal Study., Setting: REasons for Geographic And Racial Differences in Stroke cohort study., Participants: Participants included 239 individuals who were not caregivers at baseline but transitioned to providing substantial and sustained caregiving over time. They were initially matched to 241 non-caregiver comparisons on age, sex, race, education, marital status, self-rated health, and history of cardiovascular disease. Blood was drawn at baseline and approximately 9.3 years at follow-up for both groups., Measurements: Perceived Stress Scale, Center for Epidemiological Studies-Depression, inflammatory biomarkers, including high-sensitivity C-reactive protein, D dimer, tumor necrosis factor alpha receptor 1, interleukin (IL)-2, IL-6, and IL-10 taken at baseline and follow-up., Results: Although at follow-up, caregivers showed significantly greater worsening in perceived stress and depressive symptoms compared to non-caregivers, there were few significant associations between depressive symptoms or perceived stress on inflammation for either group. Inflammation, however, was associated with multiple demographic and health variables, including age, race, obesity, and use of medications for hypertension and diabetes for caregivers and non-caregivers., Conclusions: These findings illustrate the complexity of studying the associations between stress, depressive symptoms, and inflammation in older adults, where these associations may depend on demographic, disease, and medication effects. Future studies should examine whether resilience factors may prevent increased inflammation in older caregivers.

Introduction: People with African ancestry have greater stroke risk and greater heritability of stroke risk than people of other ancestries. Given the importance of nitric oxide (NO) in stroke, and recent evidence that alpha globin restricts nitric oxide release from vascular endothelial cells, we hypothesized that alpha globin gene ( HBA) deletion would be associated with reduced risk of incident ischemic stroke., Methods: We evaluated 8,947 participants self-reporting African ancestry in the national, prospective Reasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. Incident ischemic stroke was defined as non-hemorrhagic stroke with focal neurological deficit lasting ≥ 24 hours confirmed by the medical record or focal or non-focal neurological deficit with positive imaging confirmed with medical records. Genomic DNA was analyzed using droplet digital PCR to determine HBA copy number. Multivariable Cox proportional hazards regression was used to estimate the hazard ratio (HR) of HBA copy number on time to first ischemic stroke., Results: Four-hundred seventy-nine (5.3%) participants had an incident ischemic stroke over a median (IQR) of 11.0 (5.7, 14.0) years' follow-up. HBA copy number ranged from 2 to 6: 368 (4%) -α/-α, 2,480 (28%) -α/αα, 6,014 (67%) αα/αα, 83 (1%) ααα/αα and 2 (<1%) ααα/ααα. The adjusted HR of ischemic stroke with HBA copy number was 1.04; 95%CI 0.89, 1.21; p = 0.66., Conclusions: Although a reduction in HBA copy number is expected to increase endothelial nitric oxide signaling in the human vascular endothelium, HBA copy number was not associated with incident ischemic stroke in this large cohort of Black Americans.

Introduction: Rural versus urban living is a social determinant of cognitive health. We estimated the association of rural versus urban residence in the USA with incident cognitive impairment (ICI) and assessed effect heterogeneity by sociodemographic, behavioral, and clinical factors., Methods: The Reasons for Geographic and Racial Differences in Stroke Study (REGARDS) is a population-based prospective observational cohort of 30,239 adults, 57% female, 36% Black, aged 45+ years, sampled from 48 contiguous states in the USA in 2003-2007. We analyzed 20,878 participants who at baseline were cognitively intact with no history of stroke and had ICI assessed on average 9.4 years later. We classified participants' home addresses at baseline as urban (population ≥50,000), large rural (10,000-49,999), or small rural (≤9,999) by Rural-Urban Commuting Area codes. We defined ICI as ≥1.5 SD below the mean on at least 2 of the following tests: word list learning, word list delayed recall, and animal naming., Results: Participants' home addresses were 79.8% urban, 11.7% large rural, and 8.5% small rural. ICI occurred in 1,658 participants (7.9%). Small rural residents had higher odds of ICI than urban residents, adjusted for age, sex, race, region, and education (OR = 1.34 [95% CI: 1.10, 1.64]), and after further adjustment for income, health behaviors, and clinical characteristics (OR = 1.24 [95% CI: 1.02, 1.53]). Former smoking versus never, nondrinking versus light alcohol drinking, no exercise versus ≥4 times/week, CES-D depressive symptom score of 2 versus 0, and fair versus excellent self-rated health had stronger associations with ICI in small rural areas than in urban areas. For example, in urban areas, lack of exercise was not associated with ICI (OR = 0.90 [95% CI: 0.77, 1.06]); however, lack of exercise combined with small rural residence was associated with 1.45 times the odds of ICI compared with ≥4 bouts of exercise/week in urban areas (95% CI: 1.03, 2.03). Overall, large rural residence was not associated with ICI; however, black race, hypertension, and depressive symptoms had somewhat weaker associations with ICI, and heavy alcohol drinking a stronger association with ICI, in large rural areas than in urban areas., Conclusion: Small rural residence was associated with ICI among USA adults. Further research to better understand why rural residents are at higher risk for developing ICI and mechanisms to ameliorate that risk will support efforts to advance rural public health., (© 2023 S. Karger AG, Basel.)

Objectives: Positive caregiver adaptation over time may be associated with reports of positive aspects of caregiving (PAC). We examined differences in PAC by caregiving duration and social engagement, controlling for measures of distress., Methods: Participants included 283 African American or White caregivers from the Caregiving Transitions Study with a wide range of caregiving durations. PAC are defined as positive appraisals that caregivers report about their role, such as feeling appreciated or confident. We fit multivariable linear models with the total PAC score as the outcome to assess its association with years of caregiving and social engagement (social network, monthly social contact). Models were adjusted for age, sex, race, marital status, relationship to care recipient, care recipient's dementia status, perceived stress and caregiving strain., Results: Caregivers with higher social engagement reported significantly higher PAC. A non-significant trend was found in most analytic models for caregivers with longer duration of care to report higher PAC. African American caregivers reported higher PAC compared to White caregivers. Dementia caregivers reported lower PAC than non-dementia caregivers in models adjusting for demographics and social network size, but the association was attenuated with the addition of caregiving strain., Discussion: Higher social engagement and longer duration of care tend to be associated with higher PAC after adjusting for demographics and measures of distress. Future studies should aim to leverage longitudinal data to understand whether caregivers shift appraisal to positive aspects of their role and explore implementation of caregiving interventions targeting PAC in order to improve the caregiving experience.

Background: Baseline depressive symptoms are associated with subsequent adverse cardiovascular (CV) events in subjects with and without diabetes but the impact of persistent symptoms vs. improvement remains controversial., Objective: Examine long-term changes in depressive symptoms in individuals with and without diabetes and the associated risk for adverse CV events., Design: REGARDS is a prospective cohort study of CV risk factors in 30,000 participants aged 45 years and older., Participants: N = 16,368 (16.5% with diabetes mellitus) who remained in the cohort an average of 11.1 years later and who had complete data., Main Measures: Depressive symptoms were measured using the 4-item Centers for Epidemiologic Study of Depression (CES-D) questionnaire at baseline and again at a mean follow-up of 5.07 (SD = 1.66) years. Adjudicated incident stroke, coronary heart disease (CHD), CV mortality, and a composite outcome were assessed in a subsequent follow-up period of 6.1 (SD = 2.6) years., Methods: The association of changes in depressive symptoms (CES-D scores) across 5 years with incident CV events was assessed using Cox proportional hazards modeling., Key Results: Compared to participants with no depressive symptoms at either time point, participants without diabetes but with persistently elevated depressive symptoms at both baseline and follow-up demonstrated a significantly increased risk of incident stroke (HR (95% CI) = 1.84 (1.03, 3.30)), a pattern which was substantially more prevalent in blacks (HR (95% CI) = 2.64 (1.48, 4.72)) compared to whites (HR (95% CI) = 1.06 (0.50, 2.25)) and in those not taking anti-depressants (HR (95% CI) = 2.01 (1.21, 3.35)) in fully adjusted models., Conclusions: The persistence of depressive symptoms across 5 years of follow-up in participants without diabetes identifies individuals at increased risk for incident stroke. This was particularly evident in black participants and among those not taking anti-depressants., (© 2022. The Author(s) under exclusive licence to Society of General Internal Medicine.)

Background: Plasma lipids are risk factors for coronary heart disease (CHD) in part because of race-specific associations of lipids with CHD., Objectives: The purpose of this study was to understand why CHD risk equations underperform in Black adults., Methods: Between 2003 and 2007, the REGARDS (REasons for Geographic and Racial Differences in Stroke) cohort recruited 30,239 Black and White individuals aged ≥45 years from the contiguous United States. We used Cox regression models adjusted for clinical and behavioral risk factors to estimate the race-specific hazard of plasma lipid levels with incident CHD (myocardial infarction or CHD death)., Results: Among 23,901 CHD-free participants (57.8% White and 58.4% women, mean age 64 ± 9 years) over a median 10 years of follow-up, 664 and 951 CHD events occurred among Black and White adults, respectively. Low-density lipoprotein cholesterol and triglycerides were associated with increased risk of CHD in both races (P interaction by race >0.10). For sex-specific clinical HDL-C categories: low HDL-C was associated with increased CHD risk in White (HR: 1.22; 95% CI: 1.05-1.43) but not in Black (HR: 0.94; 95% CI: 0.78-1.14) adults (P interaction by race = 0.08); high HDL-C was not associated with decreased CHD events in either race (HR: 0.96; 95% CI: 0.79-1.16 for White participants and HR: 0.91; 95% CI: 0.74-1.12 for Black adults)., Conclusions: Low-density lipoprotein cholesterol and triglycerides modestly predicted CHD risk in Black and White adults. Low HDL-C was associated with increased CHD risk in White but not Black adults, and high HDL-C was not protective in either group. Current high-density lipoprotein cholesterol-based risk calculations could lead to inaccurate risk assessment in Black adults., Competing Interests: Funding Support and Author Disclosures This research project is supported by cooperative agreement U01 NS041588 co-funded by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute on Aging, National Institutes of Health, Department of Health and Human Service; and by R01HL136373 (to Drs Zakai, Minnier, and Pamir) and R01 HL080477 (to Dr Safford) from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS or the National Institute on Aging. Representatives of the NINDS were involved in the review of the manuscript but were not directly involved in the collection, management, analysis or interpretation of the data. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: The use of surrogate end points can decrease sample size while maintaining statistical power. This report considers incident stroke symptoms as a surrogate end point in a post hoc analysis of asymptomatic patients from the multicenter, randomized Carotid Revascularization Endarterectomy vs Stenting Trial (CREST)., Methods: CREST assessed stroke symptoms using the Questionnaire for Verifying Stroke-free Status (QVSS) at baseline and follow-up. While the primary analysis of CREST defined "asymptomatic" as having been free of stroke/transient ischemic attack for 180 days, herein the population was further restricted by requiring no stroke symptoms at baseline. Incident adjudicated stroke was defined the same as for the primary analysis; incident stroke symptoms was defined as developing ≥1 stroke symptom in follow-up. Treatment differences between stenting (CAS) and endarterectomy (CEA) were assessed for 3 end points: adjudicated stroke, stroke symptoms, and adjudicated stroke or stroke symptoms., Results: The cohort included 826 of the 1,181 asymptomatic patients in CREST. Adjudicated stroke events occurred in 44 patients, and incident stroke symptoms occurred in 183. Analysis of adjudicated stroke end points demonstrated a nonsignificant hazard ratio (HR) for CAS compared with CEA of 1.02 (95% CI 0.57-1.85). The corresponding HR for the incident stroke symptoms outcome was 1.54 (95% CI 1.15-2.08), and the HR for the composite outcome of adjudicated stroke or incident symptoms was 1.38 (95% CI 1.04-1.83), both significant., Discussion: The low stroke event rates in asymptomatic patients challenges the assessment of CAS-versus-CEA treatment differences. Incorporating incident stroke symptoms as a surrogate outcome increased the number of events by over 4-fold. The analysis demonstrated a previously unreported significant difference in cerebrovascular risk with CAS compared with CEA. We propose that broadening the end points of primary stroke prevention trials to include surrogate events such as incident stroke symptoms could make trials more feasible., (© 2022 American Academy of Neurology.)

Background: Individual inflammation biomarkers are associated with incident coronary heart disease (CHD) events. However, there is limited research on whether the risk for incident CHD is progressively higher with a higher number of inflammation biomarkers in abnormal levels., Methods: We used data from 15,758 Reasons for Geographic and Racial Differences in Stroke (REGARDS) study participants aged ≥45 years without a history of CHD at baseline in 2003-2007. Abnormal levels of baseline high-sensitivity C-reactive protein, leukocyte count and serum albumin were defined as ≥3.8 mg/L (3rd tertile), ≥6.3 x 10 9 cells/L (3rd tertile), and <4.0 g/dL (1st tertile), respectively. The outcome was a composite of incident myocardial infarction or CHD death., Results: Overall, 38.9% (n = 6,123) had 0, 36.6% (n = 5,774) had 1, 19.8% (n = 3,113) had 2 and 4.7% (n = 748) had 3 biomarkers of inflammation in abnormal levels. Over a median follow-up of 11.4 years, 954 (6.1%) participants had incident CHD. The rate of incident CHD per 1000 person-years for individuals with 0, 1, 2, and 3 biomarkers of inflammation in abnormal levels was 4.4 (95% confidence interval [CI]: 3.9-5.0), 6.3 (95% CI: 5.6-6.9), 8.8 (95% CI: 7.8-9.9), and 10.6 (95% CI: 8.1-13.1), respectively. Multi-variable adjusted hazard ratios for incident CHD associated with 1, 2 and 3 versus no inflammation biomarker in abnormal levels were 1.26 (95% CI: 1.07-1.49), 1.72 (95% CI: 1.43-2.07), and 1.84 (95% CI: 1.37-2.47), respectively (P-trend < .001)., Conclusions: The number of inflammation markers in abnormal levels was associated with increased risk of incident CHD after multi-variable adjustment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Sedentary behavior is associated with poor physical function in older adults, which can lead to accelerated skeletal muscle aging (sarcopenia) and premature mortality. We examined the independent and joint effects of sedentary behavior and moderate to vigorous intensity physical activity (MVPA) with measures of physical functioning., Methods: We studied 5408 participants in the REasons for Geographic and Racial Differences in Stroke study who wore a hip-mounted accelerometer over seven consecutive days (2009-2013) and had self-reported and directly observed physical function (time walk, chair stand test) measured during an in-home visit conducted from 2013 to 2016., Results: Greater sedentary time was significantly associated with poorer chair stand and timed walk scores. Substituting 30 min of sedentary time with 30 min of MVPA was associated with significant improvements in chair stands (β -0.57; P = 0.007) and timed walk (β -0.36; P = 0.01). Similar, but less robust, findings were observed for reallocations of sedentary time to light-intensity physical activity. In joint association analyses, high sedentary time in combination with low MVPA (but not in combination with high MVPA) was associated with poorer physical function compared with the referent group (low sedentary time/high MVPA; P < 0.001 for all)., Conclusions: Greater time spent being sedentary was associated with worse physical functioning outcomes. However, reallocations of sedentary time to light-intensity physical activity, and especially MVPA, were associated with more favorable physical functioning. Interventions aimed to increase MVPA and reduce sedentary behavior should be a priority, especially among populations at greatest risk for sarcopenia and physical function decline., (Copyright © 2022 by the American College of Sports Medicine.)

Objectives: Cardiac rhythm monitoring is increasingly used after stroke. We studied feasibility of telephone guided, mail-in ambulatory long-term cardiac rhythm monitoring in Black and White stroke survivors. MATERIALS AND METHODS;: We contacted 28 participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who had an ischemic stroke during follow-up. After obtaining informed consent by telephone, a noninvasive 14-day cardiac rhythm monitoring device (ZIO® XT patch; iRhythm Technologies, San Francisco, CA) was mailed to each participant. We evaluated the results of telephone consent, follow-up calls, compliance and wear time as the primary objective. Secondarily, we reported prevalence of atrial and ventricular arrhythmias., Results: The majority of those contacted (20/28 = 71%) agreed to enroll in the monitoring study. Non-participation was nominally more common in Black than White participants; 6/16 (37.5%) vs. 2/12 (17%). Of those who agreed, 15 participants (75%, 6 Black, 9 White) completed ambulatory monitoring with mean wear time 12.9 ± 2.5 days. Arrhythmias were observed in two-thirds of the 15 participants: AF in 2, brief atrial tachycardia in 12, NSVT in 2, premature ventricular contractions in 3, and pause or atrioventricular block in 2., Conclusions: Non-invasive rhythm monitoring was feasible in this pilot from a large, national cohort study of stroke survivors that employed a telephone guided, mail-in monitoring system, and these preliminary results suggest a high prevalence of arrhythmias. Increased emphasis on recruitment strategies for Black stroke survivors may be required. We demonstrated a high yield of significant cardiac arrhythmias among post-stroke participants who completed monitoring., Competing Interests: Declarations of Competing Interest RD has received grant support from iRhythm Technologies, Inc., (Copyright © 2022. Published by Elsevier Inc.)

Background and Aims: Identifying individuals at elevated risk for mortality, especially from cardiovascular disease, may help guide testing and treatment. Risk factors for mortality differ by sex and race. We investigated the association of growth hormone (GH) with all-cause and cardiovascular mortality in a racially diverse cohort in the United States., Methods: Among an age, sex and race stratified subgroup of 1046 Black and White participants from the REasons for Geographic And Racial Disparities in Stroke (REGARDS) study, 881 had GH available; values were log 2 transformed. Associations with all-cause and cardiovascular mortality were assessed in the whole subgroup, and by sex and race, using multivariable Cox-proportional hazard models and C-index., Results: The mean age was 67.4 years, 51.1% were women, and 50.2% were Black participants. The median GH was 280 (interquartile range 79-838) ng/L. There were 237 deaths and 74 cardiovascular deaths over a mean of 8.0 years. In multivariable Cox analysis, GH was associated with higher risk of all-cause mortality per doubling (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.09-1.25) and cardiovascular mortality (HR 1.21, 95% CI 1.06-1.37). The association did not differ by sex or race (interaction p > 0.05). The addition of GH to a model of clinical variables significantly improved the C-index compared to clinical model alone for all-cause and cardiovascular death., Conclusions: Higher fasting GH was associated with higher risk of all-cause and cardiovascular mortality and improved risk prediction, regardless of sex or race., (Published by Elsevier B.V.)

Background: Contemporary data on stroke epidemiology and the availability of national stroke clinical registries are important for providing evidence to improve practice and support policy decisions., Aims: To update the most current incidence, case-fatality, and mortality rates on stroke and identify national stroke clinical registries worldwide., Methods: We searched multiple databases (based on our existing search strategy) to identify new original papers, published between 1 November 2018 and 15 December 2021, that met ideal criteria for data on stroke incidence and case-fatality, and added these to the studies reported in our last review. To identify national stroke clinical registries, we updated our last search, using PubMed, from 6 February 2015 until 6 January 2022. We also screened reference lists of review papers, citation history of papers, and the gray literature. Mortality codes for International Classification of Diseases (ICD)-9 and ICD-10 were extracted from the World Health Organization (WHO) for each country providing these data. Population denominators were obtained from the United Nations (UN) or WHO (when data were unavailable in the UN database). Crude and adjusted stroke mortality rates were calculated using country-specific population denominators, and the most recent years of mortality data available for each country., Results: Since our last report in 2020, there were two countries (Chile and France) with new incidence studies meeting criteria for ideal population-based studies. New data on case-fatality were found for Chile and Kenya. The most current mortality data were available for the year 2014 (1 country), 2015 (2 countries), 2016 (11 countries), 2017 (10 countries), 2018 (19 countries), 2019 (36 countries), and 2020 (29 countries). Four countries (Libya, Solomon Islands, United Arab Emirates, and Lebanon) reported mortality data for the first time. Since our last report on registries in 2017, we identified seven more national stroke clinical registries, predominantly in high-income countries. These newly identified registries yielded limited information., Conclusions: Up-to-date data on stroke incidence, case-fatality, and mortality continue to provide evidence of disparities and the scale of burden in low- and middle-income countries. Although more national stroke clinical registries were identified, information from these newly identified registries was limited. Highlighting data scarcity or even where a country is ranked might help facilitate more research or greater policy attention in this field.

Background: The joint associations of total and intensity-specific physical activity with obesity in relation to all-cause mortality risk are unclear., Methods: We included 34 492 adults (72% women, median age 62.1 years, 2034 deaths during follow-up) in a harmonised meta-analysis of eight population-based prospective cohort studies with mean follow-up ranging from 6.0 to 14.5 years. Standard body mass index categories were cross-classified with sample tertiles of device-measured total, light-to-vigorous and moderate-to-vigorous physical activity and sedentary time. In five cohorts with waist circumference available, high and low waist circumference was combined with tertiles of moderate-to-vigorous physical activity., Results: There was an inverse dose-response relationship between higher levels of total and intensity-specific physical activity and mortality risk in those who were normal weight and overweight. In individuals with obesity, the inverse dose-response relationship was only observed for total physical activity. Similarly, lower levels of sedentary time were associated with lower mortality risk in normal weight and overweight individuals but there was no association between sedentary time and risk of mortality in those who were obese. Compared with the obese-low total physical activity reference, the HRs were 0.59 (95% CI 0.44 to 0.79) for normal weight-high total activity and 0.67 (95% CI 0.48 to 0.94) for obese-high total activity. In contrast, normal weight-low total physical activity was associated with a higher risk of mortality compared with the obese-low total physical activity reference (1.28; 95% CI 0.99 to 1.67)., Conclusions: Higher levels of physical activity were associated with lower risk of mortality irrespective of weight status. Compared with obesity-low physical activity, there was no survival benefit of being normal weight if physical activity levels were low., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the United States. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey conducted via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations and high-quality event surveillance. Extensive prepandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these data will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including postacute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term health trajectories., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)