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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.

Background: Cognitive impairment after stroke is common and is present in up to 60% of survivors. Stroke severity, indicated by both volume and location, is the most consequential predictor of cognitive impairment, with severe strokes predicting higher chances of cognitive impairment. The current investigation examines the associations of 2 stroke severity ratings and a caregiver-report of poststroke functioning with longitudinal cognitive outcomes., Methods and Results: One hundred fifty-seven caregivers and stroke survivor dyads participated in the CARES (Caring for Adults Recovering From the Effects of Stroke) project, an ancillary study of the REGARDS (Reasons for Geographic and Racial Differences in Stroke) national cohort study. The Glasgow Outcome Scale and modified Rankin Scale scores collected at hospitalization discharge were included as 2 primary predictors of cognitive impairment. The number of caregiver-reported problems and impairments at 9 months following stroke were included as a third predictor. Cognition was measured using a biennial telephone battery and included the domains of learning, memory, and executive functioning. Multiple cognitive assessments were analyzed up to 5 years poststroke, controlling for prestroke cognition and demographic variables of the stroke survivor. Separate mixed models showed significant main effects of the Glasgow Outcome Scale (b=0.3380 [95% CI, 0.14-0.5]; P =0.0009), modified Rankin Scale (b=-0.2119 [95% CI, -0.32 to -0.10]; P =0.0002), and caregiver-reported problems (b=-0.0671 [95% CI, -0.09 to -0.04]; P <0.0001) on longitudinal cognitive scores. In a combined model including all 3 predictors, only caregiver-reported problems significantly predicted cognition (b=-0.0480 [95% CI, -0.08 to -0.03]; P <0.0001)., Conclusions: These findings emphasize the importance of caregiver feedback in predicting cognitive consequences of stroke.

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.

Background: Heart failure (HF) affects >6 million US adults, with recent increases in HF hospitalizations. We aimed to investigate the association between neighborhood disadvantage and incident HF events and potential differences by diabetes status., Methods: We included 23 645 participants from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke), a prospective cohort of Black and White adults aged ≥45 years living in the continental United States (baseline 2005-2007). Neighborhood disadvantage was assessed using a Z score of 6 census tract variables (2000 US Census) and categorized as quartiles. Incident HF hospitalizations or HF-related deaths through 2017 were adjudicated. Multivariable-adjusted Cox regression was used to examine the association between neighborhood disadvantage and incident HF. Heterogeneity by diabetes was assessed using an interaction term., Results: The mean age was 64.4 years, 39.5% were Black adults, 54.9% females, and 18.8% had diabetes. During a median follow-up of 10.7 years, there were 1125 incident HF events with an incidence rate of 3.3 (quartile 1), 4.7 (quartile 2), 5.2 (quartile 3), and 6.0 (quartile 4) per 1000 person-years. Compared to adults living in the most advantaged neighborhoods (quartile 1), those living in neighborhoods in quartiles 2, 3, and 4 (most disadvantaged) had 1.30 (95% CI, 1.06-1.60), 1.36 (95% CI, 1.11-1.66), and 1.45 (95% CI, 1.18-1.79) times greater hazard of incident HF even after accounting for known confounders. This association did not significantly differ by diabetes status (interaction P =0.59). For adults with diabetes, the adjusted incident HF hazards comparing those in quartile 4 versus quartile 1 was 1.34 (95% CI, 0.92-1.96), and it was 1.50 (95% CI, 1.16-1.94) for adults without diabetes., Conclusions: In this large contemporaneous prospective cohort, neighborhood disadvantage was associated with an increased risk of incident HF events. This increase in HF risk did not differ by diabetes status. Addressing social, economic, and structural factors at the neighborhood level may impact HF prevention., Competing Interests: Disclosures Drs Safford and Carson receive investigator-initiated research support from Amgen Inc. Dr Goyal has received personal fees for medicolegal consulting on heart failure and has received honoraria from Akcea Inc and Bionest Inc. The other authors report no conflicts.

Objective: Black Americans have a greater risk of type 2 diabetes than White Americans. The proinflammatory cytokine interleukin-6 (IL-6) is implicated in diabetes pathogenesis, and IL-6 levels are higher in Black individuals. This study investigated associations of IL-6 with incident diabetes and metabolic syndrome in a biracial cohort., Research Design and Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study enrolled 30,239 Black and White adults age ≥45 years in 2003-2007, with a follow-up ∼9.5 years later. Baseline plasma IL-6 was measured in 3,399 participants at risk of incident diabetes and 1,871 at risk of metabolic syndrome. Relative risk (RR) by IL-6 was estimated with modified Poisson regression for both groups., Results: Incident diabetes occurred in 14% and metabolic syndrome in 20%; both rates rose across IL-6 quartiles. There was a three-way interaction of IL-6, race, and central adiposity for incident diabetes (P = 8 × 10-5). In Black participants with and without central adiposity, RRs were 2.02 (95% CI 1.00-4.07) and 1.66 (1.00-2.75) for the fourth compared with first IL-6 quartile, respectively. The corresponding RRs were 1.73 (0.92-3.26) and 2.34 (1.17-4.66) in White participants. The pattern was similar for IL-6 and metabolic syndrome., Conclusions: Although IL-6 was higher in Black than in White participants and those with central adiposity, the association of IL-6 with diabetes risk was statistically significant only among White participants without central adiposity. The association with metabolic syndrome risk was similarly stronger in low-risk groups. The results support the concept of interventions to lower inflammation in diabetes prevention, but to reduce race disparities, better biomarkers are needed., (© 2024 by the American Diabetes Association.)

Falls can have life-altering consequences for older adults, including extended recovery periods and compromised independence. Higher household income may mitigate the risk of falls by providing financial resources for mobility tools, remediation of environmental hazards, and needed supports, or it may buffer the impact of an initial fall on subsequent risk through improved assistance and care. Household income has not had a consistently observed association with falls in older adults; however, a segmented association may exist such that associations are attenuated above a certain income threshold. In this study, we utilized segmented negative binomial regression analysis to examine the association between household income and recurrent falls among 2,302 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study recruited between 2003 and 2007. Income-fall association segments separated by changes in slope were considered. Model results indicated a 2-segment association between household income and recurrent falls in the past year. In the range below the breakpoint, household income was negatively associated with the rate of recurrent falls across all age groups examined; in a higher income range (from $20,000-$49,999 to ≥$150,000), the association was attenuated (weaker negative trend) or reversed (positive trend). These findings point to potential benefits of ensuring that incomes for lower-income adults exceed the threshold needed to confer a reduced risk of recurrent falls., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Exposure to radon has been linked to lung cancer and other lung diseases. Although biologically plausible, research of residential radon exposure in relation to stroke risk is scarce., Methods: Study participants were from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort (n=30 239), which consisted of male and female non-Hispanic Black and White adults aged 45 and older. After excluding participants with baseline stroke and transient ischemic attack, and missing information on exposure and outcome of interest, the final sample size was 26 950. The primary outcome was time to the first ischemic stroke through September 30, 2020. County-level radon measures from Lawrence Berkeley National Laboratory were linked to each participant based on their geocoded residential history. We used Cox proportional hazards regression models with a time-dependent exposure to estimate hazard ratios and 95% CIs for the association., Results: After controlling for potential confounding factors including demographic, lifestyle, clinical variables, and PM 2.5 , radon exposure was significantly associated with incident ischemic stroke among never-smokers (hazard ratio, 1.39 [95% CI, 1.01-1.90]) but not ever-smokers. The results were generally consistent in the sensitivity analysis when using radon measures from state/Environmental Protection Agency residential radon survey., Conclusions: Findings from this study suggest that the association between residential radon exposure and incidence of ischemic stroke varies by smoking status and may be prominent in never-smokers. Further studies incorporating indoor-radon measures are needed to confirm these findings., Competing Interests: Disclosures None.

Background: Features of the physical environment may affect post-stroke recovery, but empirical evidence is limited. This study examines associations between features of the physical environment and post-stroke physical quality of life (PH-QOL)., Methods: The study sample included stroke survivors enrolled in the Caring for Adults Recovering from the Effects of Stroke project, a prospective cohort. Features of the physical environment surrounding participants' home addresses were audited using Google Earth. Audits captured information about crossings (e.g. curb-cuts; range 0-4), street segments (e.g. sidewalks; range 0-17.5), and a route (e.g. parks; range 0-27) near participants' home. Summary scores were categorized into tertials representing "few," "some," and "many" pedestrian-friendly features. Post-stroke PH-QOL was measured by the SF-12 (range 0-100) around 6 to 12-, 18-, 27-, and 36-months post-stroke. Linear mixed models were used to estimate PH-QOL over time. Chained multiple imputation was used to account for missing data., Results: Two hundred and seventy-five participants were eligible, among whom 210 had complete data. Most participants lived in areas with "few" features to promote outdoor mobility. Participants living in environments with "some" crossing features had a 4.90 (95% CI: 2.32, 7.48) higher PH-QOL score across the observation period in comparison to participants living in environments with "few" crossing features. Features of the physical environment along street segments and routes were not associated with post-stroke PH-QOL., Conclusion: Crossing features are associated with post-stroke PH-QOL. Modifying features of the physical environment at nearby crossings, such as curb-cuts, may be a promising strategy for increasing PH-QOL.

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.)

Rationale & Objective: Little information exists on the incidence of and risk factors for chronic kidney disease (CKD) in contemporary US cohorts and whether risk factors differ by race, sex, or region in the United States., Study Design: Observational cohort study., Setting & Participants: 4,198 Black and 7,799 White participants aged at least 45 years, recruited from 2003 through 2007 across the continental United States, with baseline estimated glomerular filtration rate (eGFR)>60mL/min/1.73m 2 and eGFR assessed again approximately 9 years later., Exposures: Age, sex, race (Black or White), region ("stroke belt" or other), education, income, systolic blood pressure, body mass index, diabetes, coronary heart disease, hyperlipidemia, smoking, and albuminuria., Outcomes: (1) eGFR change and (2) incident CKD defined as eGFR<60mL/min/1.73m 2 and≥40% decrease from baseline or kidney failure., Analytical Approach: Linear regression and modified Poisson regression were used to determine the association of risk factors with eGFR change and incident CKD overall and stratified by race, sex, and region., Results: Mean age of participants was 63±8 (SD) years, 54% were female, and 35% were Black. After 9.4±1.0 years of follow-up, CKD developed in 9%. In an age-, sex-, and race-adjusted model, Black race (β =-0.13; P<0.001) was associated with higher risk of eGFR change, but this was attenuated in the fully adjusted model (β=0.02; P=0.5). Stroke belt residence was independently associated with eGFR change (β =-0.10; P<0.001) and incident CKD (relative risk, 1.14 [95% CI, 1.01-1.30]). Albuminuria was more strongly associated with eGFR change (β of-0.26 vs-0.17; P=0.01 for interaction) in Black compared with White participants. Results were similar for incident CKD., Limitations: Persons of Hispanic ethnicity were excluded; unknown duration and/or severity of risk factors., Conclusions: Established CKD risk factors accounted for higher risk of incident CKD in Black versus White individuals. Albuminuria was a stronger risk factor for eGFR decrease and incident CKD in Black compared with White individuals. Living in the US stroke belt is a novel risk factor for CKD., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Several metabolite markers are independently associated with incident ischemic stroke. However, prior studies have not accounted for intercorrelated metabolite networks. We used exploratory factor analysis (EFA) to determine if metabolite factors were associated with incident ischemic stroke. Metabolites (n = 162) were measured in a case-control cohort nested in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, which included 1,075 ischemic stroke cases and 968 random cohort participants. Cox models were adjusted for age, gender, race, and age-race interaction (base model) and further adjusted for the Framingham stroke risk factors (fully adjusted model). EFA identified fifteen metabolite factors, each representing a well-defined metabolic pathway. Of these, factor 3, a gut microbiome metabolism factor, was associated with an increased risk of stroke in the base (hazard ratio per one-unit standard deviation, HR = 1.23; 95%CI = 1.15-1.31; P = 1.98 × 10 -10 ) and fully adjusted models (HR = 1.13; 95%CI = 1.06-1.21; P = 4.49 × 10 -4 ). The highest tertile had a 45% increased risk relative to the lowest (HR = 1.45; 95%CI = 1.25-1.70; P = 2.24 × 10 -6 ). Factor 3 was also associated with the Southern diet pattern, a dietary pattern previously linked to increased stroke risk in REGARDS (β = 0.11; 95%CI = 0.03-0.18; P = 8.75 × 10 -3 ). These findings highlight the role of diet and gut microbial metabolism in relation to incident ischemic stroke.

Background and Objectives: In the United States, the risk of stroke is greater among Black compared with that among White individuals. However, the reasons for the difference in stroke incidence are not fully elucidated. We aimed to identify metabolites that account for higher prevalent hypertension and incident ischemic stroke among Black adults., Methods: We used a stroke case cohort nested within the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Targeted metabolomic profiling of 162 plasma metabolites was performed by liquid chromatography-tandem mass spectrometry. We identified metabolites that were associated with prevalent hypertension and incident ischemic stroke and mediated the relationship between hypertension and ischemic stroke by weighted logistic regression, Cox proportional hazard model, and inverse odds ratio weighting mediation analysis., Results: Incident ischemic stroke cases adjudicated through April 1, 2019 (n = 1,075) were included in the study. The random cohort sample was derived from the full cohort using stratified sampling (n = 968). Among 162 metabolites, gluconic acid was associated with prevalent hypertension in Black adults (odds ratio [OR] 1.86, 95% CI 1.39-2.47, p = 2.58 × 10 -5 ) but not in White adults (OR 1.00, 95% CI 0.80-1.24, p = 0.97; p for interaction = 4.57 × 10 -4 ). Gluconic acid also demonstrated an association with incident ischemic stroke among Black participants (hazard ratio [HR] 1.53, 95% CI 1.28-1.81, p = 1.76 × 10 -6 ) but not White participants (HR 1.16, 95% CI 1.00-1.34, p = 0.057; p for interaction = 0.019). In mediation analysis, gluconic acid mediated 25.4% (95% CI 4.1%-46.8%, p = 0.02) of the association between prevalent hypertension and incident ischemic stroke among Black individuals. Specific socioeconomic factors were linked to elevated gluconic acid level among Black adults in multivariable analysis, including a Southern dietary pattern (β = 0.18, 95% CI 0.08-0.28, p < 0.001), lower educational attainment (β = 0.45, 95% CI 0.19-0.72, p = 0.001), and a lack of exercise (β = 0.26, 95% CI 0.01-0.51, p = 0.045)., Discussion: Gluconic acid is associated with prevalent hypertension and incident ischemic stroke and mediates the relationship between hypertension and ischemic stroke in Black but not White adults. Gluconic acid is a biomarker that is associated with social determinants of health including a Southern diet, low educational attainment, and low physical activity., (© 2023 American Academy of Neurology.)

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is prevalent and may affect cognitive function. We studied associations of NAFLD with risk of cognitive impairment. Secondarily we evaluated liver biomarkers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), their ratio, and gamma-glutamyl transpeptidase)., Methods: In a prospective cohort study, the REasons for Geographic and Racial Differences in Stroke, among 30,239 black and white adults aged ≥45,495 cases of incident cognitive impairment were identified over 3.4 years follow up. Cognitive impairment was identified as new impairment in two of three cognitive tests administered every two years during follow up; word list learning and recall, and verbal fluency. 587 controls were selected from an age, race, sex-stratified sample of the cohort. The fatty liver index was used to define baseline NAFLD. Liver biomarkers were measured using baseline blood samples., Results: NAFLD at baseline was associated with a 2.01-fold increased risk of incident cognitive impairment in a minimally adjusted model (95% CI 1.42, 2.85). The association was largest in those aged 45-65 (p interaction by age = 0.03), with the risk 2.95-fold increased (95% CI 1.05, 8.34) adjusting for cardiovascular, stroke and metabolic risk factors. Liver biomarkers were not associated with cognitive impairment, except AST/ALT >2, with an adjusted OR 1.86 (95% CI 0.81, 4.25) that did not differ by age., Conclusions: A laboratory-based estimate of NAFLD was associated with development of cognitive impairment, particularly in mid-life, with a tripling in risk. Given its high prevalence, NAFLD may be a major reversible determinant of cognitive health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cushman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background 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.)

Importance: Stroke is the fifth-highest cause of death in the US and a leading cause of serious long-term disability with particularly high risk in Black individuals. Quality risk prediction algorithms, free of bias, are key for comprehensive prevention strategies., Objective: To compare the performance of stroke-specific algorithms with pooled cohort equations developed for atherosclerotic cardiovascular disease for the prediction of new-onset stroke across different subgroups (race, sex, and age) and to determine the added value of novel machine learning techniques., Design, Setting, and Participants: Retrospective cohort study on combined and harmonized data from Black and White participants of the Framingham Offspring, Atherosclerosis Risk in Communities (ARIC), Multi-Ethnic Study for Atherosclerosis (MESA), and Reasons for Geographical and Racial Differences in Stroke (REGARDS) studies (1983-2019) conducted in the US. The 62 482 participants included at baseline were at least 45 years of age and free of stroke or transient ischemic attack., Exposures: Published stroke-specific algorithms from Framingham and REGARDS (based on self-reported risk factors) as well as pooled cohort equations for atherosclerotic cardiovascular disease plus 2 newly developed machine learning algorithms., Main Outcomes and Measures: Models were designed to estimate the 10-year risk of new-onset stroke (ischemic or hemorrhagic). Discrimination concordance index (C index) and calibration ratios of expected vs observed event rates were assessed at 10 years. Analyses were conducted by race, sex, and age groups., Results: The combined study sample included 62 482 participants (median age, 61 years, 54% women, and 29% Black individuals). Discrimination C indexes were not significantly different for the 2 stroke-specific models (Framingham stroke, 0.72; 95% CI, 0.72-073; REGARDS self-report, 0.73; 95% CI, 0.72-0.74) vs the pooled cohort equations (0.72; 95% CI, 0.71-0.73): differences 0.01 or less (P values >.05) in the combined sample. Significant differences in discrimination were observed by race: the C indexes were 0.76 for all 3 models in White vs 0.69 in Black women (all P values <.001) and between 0.71 and 0.72 in White men and between 0.64 and 0.66 in Black men (all P values ≤.001). When stratified by age, model discrimination was better for younger (<60 years) vs older (≥60 years) adults for both Black and White individuals. The ratios of observed to expected 10-year stroke rates were closest to 1 for the REGARDS self-report model (1.05; 95% CI, 1.00-1.09) and indicated risk overestimation for Framingham stroke (0.86; 95% CI, 0.82-0.89) and pooled cohort equations (0.74; 95% CI, 0.71-0.77). Performance did not significantly improve when novel machine learning algorithms were applied., Conclusions and Relevance: In this analysis of Black and White individuals without stroke or transient ischemic attack among 4 US cohorts, existing stroke-specific risk prediction models and novel machine learning techniques did not significantly improve discriminative accuracy for new-onset stroke compared with the pooled cohort equations, and the REGARDS self-report model had the best calibration. All algorithms exhibited worse discrimination in Black individuals than in White individuals, indicating the need to expand the pool of risk factors and improve modeling techniques to address observed racial disparities and improve model performance.

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.)

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.)

Introduction: Post-stroke physical activity has widespread health benefits. Environmental exposures may shape post-stroke physical activity behavior. This study investigates the relationships between environmental exposures and post-stroke physical activity., Methods: Stroke survivors (n=374) from a cohort of Black and White adults with post-stroke accelerometer data (2009-2013) were eligible for this study. Participants' home addresses were linked with secondary data to capture environmental characteristics, including annual density of neighborhood resources (e.g., parks, physical activity facilities, and intellectual stimulation destinations), 2010 neighborhood SES, 2010 neighborhood crime, and daily information on extremely cold days. Post-stroke light physical activity and moderate-to-vigorous physical activity were captured using accelerometers over a 7-day period. Linear regression and 2-part/hurdle models were used to estimate the relationship between the density of neighborhood resources with light physical activity and with moderate-to-vigorous physical activity, respectively. Analyses were conducted in 2021., Results: A 10% increase in the number of extremely cold days was associated with 6.37 fewer minutes of daily light physical activity (95% CI= -11.37, -1.37). A 1-SD increase in neighborhood SES was associated with greater odds (OR=1.10, 95% CI=1.02, 1.19) of doing any moderate-to-vigorous physical activity. Among participants obtaining any moderate-to-vigorous physical activity, a 1-unit (count/km 2 ) increase in destinations for intellectual stimulation was associated with 0.99 (95% CI=0.02, 1.97) more minutes of daily moderate-to-vigorous physical activity. All other environmental exposures were not associated with post-stroke light physical activity or moderate-to-vigorous physical activity., Conclusions: Environmental exposures may facilitate physical activity participation among stroke survivors. This study found that weather, neighborhood SES, and proximity to destinations for intellectual stimulation were associated with physical activity over and above individual factors., (Copyright © 2022 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: We previously described the magnitude of rural-urban differences in the prevalence of stroke risk factors and stroke mortality. In this report, we sought to extend the understanding of rural-urban differences in the prevalence of stroke risk factors by using an enhanced definition of rural-urban status and assessing the impact of neighborhood socioeconomic status (nSES) on risk factor differences., Methods: This analysis included 28,242 participants without a history of stroke from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. Participants were categorized into the 6-level ordinal National Center for Health Statistics Urban-Rural Classification Scheme. The prevalence of stroke risk factors (hypertension, diabetes, smoking, atrial fibrillation, left ventricular hypertrophy, and heart disease) was assessed across the rural-urban scale with adjustment for demographic characteristics and further adjustment for nSES score., Findings: Hypertension, diabetes, and heart disease were more prevalent in rural than urban regions. Higher odds were observed for these risk factors in the most rural compared to the most urban areas (odds ratios [95% CI]: 1.25 [1.11-1.42] for hypertension, 1.15 [0.99-1.33] for diabetes, and 1.19 [1.02-1.39] for heart disease). Adjustment for nSES score partially attenuated the odds of hypertension and heart disease with rurality, completely attenuated the odds of diabetes, and unmasked an association of current smoking., Conclusions: Some of the higher stroke mortality in rural areas may be due to the higher burden of stroke risk factors in rural areas. Lower nSES contributed most notably to rural-urban differences for diabetes and smoking., (© 2021 National Rural Health Association.)

Background and Objectives: Both genetic and environmental factors contribute to stroke risk. We sought to identify novel metabolites associated with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort and determine whether they reflected genetic or environmental variation., Methods: This was a stroke case-cohort observational study nested in REGARDS. Cases were defined as incident stroke and metabolomic profiles were compared to a randomly selected control cohort. In baseline plasma samples, 162 metabolites were measured using liquid chromatography-tandem mass spectrometry. Cox proportional hazards models were adjusted for age, sex, race, and age by race in the base model. Fully adjusted models included traditional stroke risk factors. Mediation analyses conducted for these stroke risk factors used the metabolite as mediator. Genome-wide associations with the leading candidate metabolites were calculated using array data. Replication analyses in the Jackson Heart Study (JHS) were conducted using random effects meta-analysis., Results: There were 2,043 participants who were followed over an average period of 7.1 years, including 1,075 stroke cases and 968 random controls. Nine metabolites were associated with stroke in the base model, 8 of which were measured and remained significant in meta-analysis with JHS. In the fully adjusted model in REGARDS, guanosine (hazard ratio [HR] 1.34, 95% CI 1.18-1.53; p = 7.26 × 10 -6 ) and pseudouridine (HR 1.28, 95% CI 1.13-1.45; p = 1.03 × 10 -4 ) were associated with incident ischemic stroke following Bonferroni adjustment. Guanosine also partially mediated the relationship between hypertension and stroke (17.6%) and pseudouridine did not mediate any risk factor. Genome-wide association analysis identified loci rs34631560 and rs34631560 associated with pseudouridine, but these did not explain the association of pseudouridine with stroke., Discussion: Guanosine and pseudouridine are nucleosides associated with incident ischemic stroke independently of other risk factors. Genetic and mediation analyses suggest that environmental exposures rather than genetic variation link nucleoside levels to stroke risk., Classification of Evidence: This study provides Class II evidence that guanosine and pseudouridine are associated with incident stroke., (© 2022 American Academy of Neurology.)

Socioeconomic status (SES) is a well-established determinant of health. Disparities in stress are thought to partially account for SES-health disparities. We tested whether multiple indicators of SES show similar associations with psychological stress and whether race, sex, and geographic region moderate associations. Participants (n = 26,451) are from a well-characterized national cohort of Black and White US adults aged 45 years or older. Psychological stress was measured using the 4-item perceived stress scale. Income was assessed as annual household income and education as highest level of education completed. Occupation was assessed during a structured interview and subsequently coded hierarchically. For all sex-race-region groups, the largest SES-stress associations were for income and the smallest were for occupation. Race moderated SES-stress associations, such that income and education were more closely associated with stress in Black adults than White adults. Additionally, education was more strongly associated with stress in individuals living in the stroke belt region. Black Americans with lower income and education reported greater psychological stress and may be at higher risk for disease through stress-related pathways. Thus, which SES indicator is examined and for whom may alter the magnitude of the association between SES and psychological stress., (© 2021 John Wiley & Sons Ltd.)

Background: Studies have shown neighborhood walkability is associated with obesity. To advance this research, study designs involving longer follow-up, broader geographic regions, appropriate neighborhood characterization, assessment of exposure length and severity, and consideration of stayers and movers are needed. Using a cohort spanning the conterminous United States, this study examines the longitudinal relationship between a network buffer-derived, duration-weighted neighborhood walkability measure and two adiposity-related outcomes., Methods: This study included 12,846 Black/African American and White adults in the REasons for Geographic And Racial Differences in Stroke study. Body mass index (BMI) and waist circumference (WC) were assessed at baseline and up to 13.3 years later (M (SD) = 9.4 (1.0) years). BMI and WC were dichotomized. Walk Score® was duration-weighted based on time at each address and categorized as Very Car-Dependent, Car-Dependent, Somewhat Walkable, Very Walkable, and Walker's Paradise. Unadjusted and adjusted logistic regression models tested each neighborhood walkability-adiposity association. Adjusted models controlled for demographics, health factors, neighborhood socioeconomic status, follow-up time, and either baseline BMI or baseline WC. Adjusted models also tested for interactions. Post-estimation Wald tests examined whether categorical variables had coefficients jointly equal to zero. Orthogonal polynomial contrasts tested for a linear trend in the neighborhood walkability-adiposity relationships., Results: The odds of being overweight/obese at follow-up were lower for residents with duration-weighted Walk Score® values in the Walker's Paradise range and residents with values in the Very Walkable range compared to residents with values in the Very Car-Dependent range. Residents with duration-weighted Walk Score® values classified as Very Walkable had significantly lower odds of having a moderate-to-high risk WC at follow-up relative to those in the Very Car-Dependent range. For both outcomes, the effects were small but meaningful. The negative linear trend was significant for BMI but not WC., Conclusion: People with cumulative neighborhood walkability scores in the Walker's Paradise range were less likely to be overweight/obese independent of other factors, while people with scores in the Very Walkable range were less likely to be overweight/obese and less likely to have a moderate-to-high risk WC. Addressing neighborhood walkability is one approach to combating obesity., (© 2022. The Author(s).)

The Southern dietary pattern, derived within the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, is characterised by high consumption of added fats, fried food, organ meats, processed meats and sugar-sweetened beverages and is associated with increased risk of several chronic diseases. The aim of the present study was to identify characteristics of individuals with high adherence to this dietary pattern. We analysed data from REGARDS, a national cohort of 30 239 black and white adults ≥45 years of age living in the USA. Dietary data were collected using the Block 98 FFQ. Multivariable linear regression was used to calculate standardised beta coefficients across all covariates for the entire sample and stratified by race and region. We included 16 781 participants with complete dietary data. Among these, 34·6 % were black, 45·6 % male, 55·2 % resided in stroke belt region and the average age was 65 years. Black race was the factor with the largest magnitude of association with the Southern dietary pattern (Δ = 0·76 sd, P < 0·0001). Large differences in Southern dietary pattern adherence were observed between black participants and white participants in the stroke belt and non-belt (stroke belt Δ = 0·75 sd, non-belt Δ = 0·77 sd). There was a high consumption of the Southern dietary pattern in the US black population, regardless of other factors, underlying our previous findings showing the substantial contribution of this dietary pattern to racial disparities in incident hypertension and stroke.

Objective: To summarize overall patterns of the impact of neighborhood socioeconomic status (nSES) on stroke incidence and uncover potential gaps in the literature, we conducted a systematic review of studies examining the association between nSES and stroke incidence, independent of individual SES., Methods: Four electronic databases and reference lists of included articles were searched, and corresponding authors were contacted to locate additional studies. A keyword search strategy included the 3 broad domains of neighborhood, SES, and stroke. Eight studies met our inclusion criteria (e.g., nSES as an exposure, individual SES as a covariate, and stroke incidence as an outcome). We coded study methodology and findings across the 8 studies., Results: The results provide evidence for the overall nSES and stroke incidence association in Sweden and Japan, but not within the United States. Findings were inconclusive when examining the nSES-stroke incidence association stratified by race. We found evidence for the mediating role of biological factors in the nSES-stroke incidence association., Conclusions: Higher neighborhood disadvantage was found to be associated with higher stroke risk, but it was not significant in all the studies. The relationship between nSES and stroke risk within different racial groups in the United States was inconclusive. Inconsistencies may be driven by differences in covariate adjustment (e.g., individual-level sociodemographic characteristics and neighborhood-level racial composition). Additional research is needed to investigate potential intermediate and modifiable factors of the association between nSES and stroke incidence, which could serve as intervention points., (© 2021 American Academy of Neurology.)

Objective: To examine if the association between higher A1C and risk of cardiovascular disease (CVD) among adults with and without diabetes is modified by racial residential segregation., Research Design and Methods: The study used a case-cohort design, which included a random sample of 2,136 participants at baseline and 1,248 participants with incident CVD (i.e., stroke, coronary heart disease [CHD], and fatal CHD during 7-year follow-up) selected from 30,239 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants originally assessed between 2003 and 2007. The relationship of A1C with incident CVD, stratified by baseline diabetes status, was assessed using Cox proportional hazards models adjusting for demographics, CVD risk factors, and socioeconomic status. Effect modification by census tract-level residential segregation indices (dissimilarity, interaction, and isolation) was assessed using interaction terms., Results: The mean age of participants in the random sample was 64.2 years, with 44% African American, 59% female, and 19% with diabetes. In multivariable models, A1C was not associated with CVD risk among those without diabetes (hazard ratio [HR] per 1% [11 mmol/mol] increase, 0.94 [95% CI 0.76-1.16]). However, A1C was associated with an increased risk of CVD (HR per 1% increase, 1.23 [95% CI 1.08-1.40]) among those with diabetes. This A1C-CVD association was modified by the dissimilarity ( P < 0.001) and interaction ( P = 0.001) indices. The risk of CVD was increased at A1C levels between 7 and 9% (53-75 mmol/mol) for those in areas with higher residential segregation (i.e., lower interaction index). In race-stratified analyses, there was a more pronounced modifying effect of residential segregation among African American participants with diabetes., Conclusions: Higher A1C was associated with increased CVD risk among individuals with diabetes, and this relationship was more pronounced at higher levels of residential segregation among African American adults. Additional research on how structural determinants like segregation may modify health effects is needed., (© 2021 by the American Diabetes Association.)

Background: The majority of people with chronic kidney disease (CKD) are unaware of their kidney disease. Assessing the clinical significance of increasing CKD awareness has critical public health and healthcare delivery implications. Whether CKD awareness among persons with CKD is associated with longitudinal health behaviors, disease management, and health outcomes is unknown., Methods: We analyzed data from participants with CKD in the REasons for Geographic And Racial Differences in Stroke study, a national, longitudinal, population-based cohort. Our predictor was participant CKD awareness. Outcomes were (1) health behaviors (smoking avoidance, exercise, and nonsteroidal anti-inflammatory drug use); (2) CKD management indicators (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, statin use, systolic blood pressure, fasting blood glucose, and body mass index); (3) change in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR); and (4) health outcomes (incident end-stage kidney disease [ESKD], coronary heart disease [CHD], stroke, and death). Logistic and linear regressions were used to examine the association of baseline CKD awareness with outcomes of interest, adjusted for CKD stage and participant demographic and clinical factors., Results: Of 6,529 participants with baseline CKD, 285 (4.4%) were aware of their CKD. Among the 3,586 participants who survived until follow-up (median 9.5 years), baseline awareness was not associated with subsequent odds of health behaviors, CKD management indicators, or changes in eGFR and UACR in adjusted analyses. Baseline CKD awareness was associated with increased risk of ESKD (adjusted hazard ratio [aHR] 1.44; 95% CI 1.08-1.92) and death (aHR 1.18; 95% CI 1.00-1.39), but not with subsequent CHD or stroke, in adjusted models., Conclusions: Individuals aware of their CKD were more likely to experience ESKD and death, suggesting that CKD awareness reflects disease severity. Most persons with CKD, including those that are high-risk, remain unaware of their CKD. There was no evidence of associations between baseline CKD awareness and longitudinal health behaviors, CKD management indicators, or eGFR decline and albuminuria., (© 2020 S. Karger AG, Basel.)

Background: The neuropeptide neurotensin (NT) has been linked to cardiometabolic disease. Cardiovascular risk factors are being recognized as risk factors for cognitive impairment., Objective: To examine the association of the stable precursor of NT, pro-neurotensin/neuromedin N (pro-NT/NMN), with incident cognitive impairment (ICI)., Methods: We conducted a prospective nested case-control study in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. In 2003-2007, REGARDS enrolled 30,239 Black and White adults aged ≥45 years. ICI was identified using a 3-test cognitive battery administered biannually. Baseline pro-NT/NMN was measured by immunoassay in 393 cases of ICI and 490 controls after 3.4 years follow up. Multivariable logistic regression was used to calculate odds ratios (OR) of ICI by pro-NT/NMN quartiles. Race, age, and sex differences were studied with stratified models and interaction testing., Results: Pro-NT/NMN was higher in Black participants and those with hypertension and diabetes. Women with a 4th versus 1st-quartile pro-NT/NMN had 2.28-fold increased odds of ICI (95% CI 1.08-4.78) after adjusting for risk factors and incident stroke. There was no association of higher pro-NT/NMN quartiles with ICI in the overall group or men. There were no race or age differences in associations., Conclusion: In this biracial population-based study, elevated systemic pro-NT/NMN was associated with more than doubled risk of ICI in women but not men. Others reported sex-specific associations in women for cardiovascular mortality and diabetes with higher pro-NT/NMN, supporting a role for future research on sex differences in the neurotensinergic system.

Background and Purpose- Persistent depression after ischemic stroke is common in stroke survivors and may be even higher in family caregivers, but few studies have examined depressive symptom levels and their predictors in patient and caregiver groups simultaneously. Methods- Stroke survivors and their family caregivers (205 dyads) were enrolled from the national REGARDS study (Reasons for Geographic and Racial Differences in Stroke) into the CARES study (Caring for Adults Recovering from the Effects of Stroke) ≈9 months after a first-time ischemic stroke. Demographically matched stroke-free dyads (N=205) were also enrolled. Participants were interviewed by telephone, and depressive symptoms were assessed with the 20-item Center for Epidemiological Studies-Depression scale. Results- Significant elevations in depressive symptoms ( Ps <0.03) were observed for stroke survivors (M=8.38) and for their family caregivers (M=6.42) relative to their matched controls (Ms=5.18 and 4.62, respectively). Stroke survivors reported more symptoms of depression than their caregivers ( P =0.008). No race or sex differences were found, but differential prediction of depressive symptom levels was found across patients and caregivers. Younger age and having an older caregiver were associated with more depressive symptoms in stroke survivors while being a spouse caregiver and reporting fewer positive aspects of caregiving were associated with more depressive symptoms in caregivers. The percentage of caregivers at risk for clinically significant depression was lower in this population-based sample (12%) than in previous studies of caregivers from convenience or clinical samples. Conclusions- High depressive symptom levels are common 9 months after first-time ischemic strokes for stroke survivors and family caregivers, but rates of depressive symptoms at risk for clinical depression were lower for caregivers than previously reported. Predictors of depression differ for patients and caregivers, and standards of care should incorporate family caregiving factors.

Objective: Given temporal changes in diabetes prevalence and stroke incidence, this study investigated age, race, and sex differences in the diabetes-stroke association in a contemporary prospective cohort, the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study., Research Design and Methods: We included 23,002 non-Hispanic black and white U.S. adults aged ≥45 years without prevalent stroke at baseline (2003-2007). Diabetes was defined as fasting glucose ≥126 mg/dL, random glucose ≥200 mg/dL, or use of glucose-lowering medication. Incident stroke events were expert adjudicated and available through September 2017., Results: The prevalence of diabetes was 19.1% at baseline. During follow-up, 1,018 stroke events occurred. Among adults aged <65 years, comparing those with diabetes to those without diabetes, the risk of stroke was increased for white women (hazard ratio [HR] 3.72 [95% CI 2.10-6.57]), black women (HR 1.88 [95% CI 1.22-2.90]), and white men (HR 2.01 [95% CI 1.27-3.27]) but not black men (HR 1.27 [95% CI 0.77-2.10]) after multivariable adjustment. Among those aged ≥65 years, diabetes increased the risk of stroke for white women and black men, but not black women (HR 1.05 [95% CI 0.74-1.48]) or white men (HR 0.86 [95% CI 0.62-1.21])., Conclusions: In this contemporary cohort, the diabetes-stroke association varied by age, race, and sex together, with a more pronounced effect observed among adults aged <65 years. With the recent increase in the burden of diabetes complications at younger ages in the U.S., additional efforts are needed earlier in life for stroke prevention among adults with diabetes., (© 2019 by the American Diabetes Association.)

Objective: We studied circulating interleukin (IL)-6, IL-8, and IL-10 concentrations and incident ischemic stroke risk in a biracial cohort, and determined if these cytokines mediated the racial disparity in stroke incidence affecting the black population., Methods: The Reasons for Geographic and Racial Differences in Stroke study enrolled 30,237 black and white men and women age ≥45 in 2003-2007. We measured baseline IL-6, IL-8, and IL-10 in a case-cohort study of 557 participants with incident stroke over 5.4 years and 951 participants in a cohort sample., Results: IL-6, but not IL-8 or IL-10, was higher in cases compared to the cohort sample (mean 4.5 vs 3.7 ng/mL; p < 0.001). Only IL-6 was associated with stroke risk factors. Adjusting for age, sex, and race, the hazard ratio (HR; 95% confidence interval) for incident stroke for the highest vs lowest quartile of IL-6 was 2.4 (1.6-3.4). HRs for the highest vs lowest quartiles of IL-8 and IL-10 were 1.5 (1.0-2.1) and 1.4 (1.0-1.9), respectively. After additional adjustment for stroke risk factors, only higher IL-6 remained associated with stroke risk (HR 2.0; 1.2-3.1). Associations did not differ by race. Mediation analyses showed that IL-6 mediated the black-white disparity in stroke risk, but mediation was via IL-6 associations with stroke risk factors., Conclusions: In this biracial population-based sample, IL-6 was strongly associated with risk of incident stroke and mediated the racial disparity in stroke via inflammatory effects of risk factors. Further study on the clinical utility of IL-6 measurement in stroke risk assessment would be helpful., (© 2019 American Academy of Neurology.)

We examined whether the sex differences in atrial fibrillation (AF) is related to difference in risk factors leading to AF or due to a differential impact of the same risk factors in 11,806 participants (55.2 % women) from the REGARDS study. Incident AF was ascertained by electrocardiograms and medical history at a follow-up examination. Backwards elimination logistic regression was used to identify AF risk factors in men and women, separately. Over a median follow-up of 9.0years, 588 (11.1%) men and 428 (6.6%) women (p value <0.001) developed AF. Men had a higher risk of AF than women (age and race adjusted odds ratio [OR] [95% confidence interval (CI)]: 1.61 [1.26, 1.75]). Age, white race, height, weight, use of blood pressure lowering medications and history of cardiovascular disease were identified by backward elimination as AF risk factors shared by both sexes. On the other hand, diabetes was an AF risk factor in women but not in men. Among the shared risk factors between men and women, only age showed a stronger association in women than in men [Interaction p-value = 0.003]. Adjustment for the shared risk factors eliminated the sex difference in AF risk (OR [95% CI]: 0.90 [0.74, 1.09]), which was more noticeable in those younger than the median age (62 years) compared to those who were older (interaction p value 0.003). In conclusion, women and men share several AF risk factors, and these shared risk factors explain the sex differences. However, age association with AF differs by sex, and age modifies the associations between sex and other AF risk factors., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Importance: Race-specific and sex-specific stroke risk varies across the lifespan, yet few reports describe sex differences in stroke risk separately in black individuals and white individuals., Objective: To examine incidence and risk factors for ischemic stroke by sex for black and white individuals., Design, Setting, and Participants: This prospective cohort study included participants 45 years and older who were stroke-free from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, enrolled from the continental United States 2003 through 2007 with follow-up through October 2016. Data were analyzed from March 2018 to September 2018., Exposures: Sex and race., Main Outcomes and Measures: Physician-adjudicated incident ischemic stroke, self-reported race/ethnicity, and measured and self-reported risk factors., Results: A total of 25 789 participants (14 170 women [54.9%]; 10 301 black individuals [39.9%]) were included. Over 222 120 person-years of follow-up, 939 ischemic strokes occurred: 159 (16.9%) in black men, 326 in white men (34.7%), 217 in black women (23.1%), and 237 in white women (25.2%). Between 45 and 64 years of age, white women had 32% lower stroke risk than white men (incidence rate ratio [IRR], 0.68 [95% CI, 0.49-0.94]), and black women had a 28% lower risk than black men (IRR, 0.72 [95% CI, 0.52-0.99]). Lower stroke risk in women than men persisted at age 65 through 74 years in white individuals (IRR, 0.71 [95% CI, 0.55-0.94]) but not in black individuals (IRR, 0.94 [95% CI, 0.68-1.30]); however, the race-sex interaction was not significant. At 75 years and older, there was no sex difference in stroke risk for either race. For white individuals, associations of systolic blood pressure (women: hazard ratio [HR], 1.13 [95% CI, 1.05-1.22]; men: 1.04 [95% CI, 0.97-1.11]; P = .099), diabetes (women: HR, 1.84 [95% CI, 1.35-2.52]; men: 1.13 [95% CI, 0.86-1.49]; P = .02), and heart disease (women: HR, 1.76 [95% CI, 1.30-2.39]; men, 1.26 [95% CI, 0.99-1.60]; P = .09) with stroke risk were larger for women than men, while antihypertensive medication use had a smaller association in women than men (women: HR, 1.17 [95% CI, 0.89-1.54]; men: 1.61 [95% CI, 1.29-2.03]; P = .08). In black individuals, there was no evidence of a sex difference for any risk factors., Conclusions and Relevance: For both races, at age 45 through 64 years, women were at lower stroke risk than men, and there was no sex difference at 75 years or older; however, the sex difference pattern may differ by race from age 65 through 74 years. The association of risk factors on stroke risk differed by race-sex groups. While the need for primordial prevention, optimal management, and control of risk factors is universal across all age, racial/ethnic, and sex groups, some demographic subgroups may require earlier and more aggressive strategies.

Sepsis - syndrome of infection complicated by organ dysfunction - is responsible for over 750 000 hospitalisations and 200 000 deaths in the USA annually. Despite potential nutritional benefits, the association of diet and sepsis is unknown. Therefore, we sought to determine the association between adherence to a Mediterranean-style diet (Med-style diet) and long-term risk of sepsis in the REasons for Geographic Differences in Stroke (REGARDS) cohort. We analysed data from REGARDS, a population-based cohort of 30 239 community-dwelling adults age ≥45 years. We determined dietary patterns from a baseline FFQ. We defined Med-style diet as a high consumption of fruit, vegetables, legumes, fish, cereal and low consumption of meat, dairy products, fat and alcohol categorising participants into Med-style diet tertiles (low: 0-3, moderate: 4-5, high: 6-9). We defined sepsis events as hospital admission for serious infection and at least two systematic inflammatory response syndrome criteria. We used Cox proportional hazard models to determine the association between Med-style diet tertiles and first sepsis events, adjusting for socio-demographics, lifestyle factors, and co-morbidities. We included 21 256 participants with complete dietary data. Dietary patterns were: low Med-style diet 32·0 %, moderate Med-style diet 42·1 % and high Med-style diet 26·0 %. There were 1109 (5·2 %) first sepsis events. High Med-style diet was independently associated with sepsis risk; low Med-style diet referent, moderate Med-style diet adjusted hazard ratio (HR) 0·93 (95 % CI 0·81, 1·08), high Med-style diet adjusted HR=0·74 (95 % CI 0·61, 0·88). High Med-style diet adherence is associated with lower risk of sepsis. Dietary modification may potentially provide an option for reducing sepsis risk.

Importance: African Americans and individuals of African ancestry have a higher risk of stroke compared with non-Hispanic white individuals. Identifying the source of this disparity could provide an opportunity for clinical stroke risk stratification and more targeted therapy. Whether sickle cell trait (SCT) is an indicator of increased risk of ischemic stroke among African Americans is still unclear., Objective: To examine whether SCT is associated with a higher risk of incident ischemic stroke among African Americans., Design, Setting, and Participants: This meta-analysis assessed the association of SCT with the risk of incident ischemic stroke. Four large, prospective, population-based studies with African American cohorts were assessed: Jackson Heart Study (September 1, 2005, through December 31, 2012), Multi-Ethnic Study of Atherosclerosis (July 1, 2002, through December 31, 2012), Reasons for Geographic and Racial Differences in Stroke (January 1, 2003, through December 31, 2014), and Women's Health Initiative (October 1, 1998, through December 31, 2012). Using a Cox proportional hazards regression model adjusted for major stroke risk factors, this study estimated the hazard ratio for incident ischemic stroke associated with SCT. Data analysis was performed from July 10, 2016, to February 2, 2017., Interventions or Exposures: Participants' SCT status determined by polymerase chain reaction assay genotyping or a combination of whole-exome sequencing and imputation., Main Outcomes and Measures: Incident ischemic stroke., Results: This meta-analysis included 19 464 African American individuals (1520 with SCT, 17 944 without SCT, and 620 with ischemic stroke) from 4 studies, with a mean (SD) age of 60.0 (13.0) years (5257 [27.0%] men and 14 207 [73.0%] women). No differences were found in the distribution of risk factors for ischemic stroke comparing participants with and those without SCT at study visit 1 in each cohort. The crude incidence of ischemic stroke was 2.9 per 1000 person-years (95% CI, 2.2-4.0 per 1000 person-years) among those with SCT and 3.2 per 1000 person-years (95% CI, 2.7-3.8 per 1000 person-years) among those without SCT. After stroke risk factors were adjusted for, the hazard ratio of incident ischemic stroke independently associated with SCT in the meta-analysis of all 4 cohorts was 0.80 (95% CI, 0.47-1.35; P = .82). The results of the meta-analysis were similar to those of individual cohorts, in which the results were also similar., Conclusions and Relevance: Sickle cell trait may not be associated with incidence of ischemic stroke among African Americans. The results of this study suggest performing a more thorough clinical evaluation of a stroke patient with SCT rather than assuming that SCT is the etiologic factor for the stroke.

Background:  Haemostatic balance represented by low protein C (PC) and elevated factor VIII (FVIII) has been inconsistently associated with stroke and coronary heart disease (CHD) risk., Objective:  This article assesses whether an elevated FVIII and a low PC would increase cardiovascular risk more than either individually., Patients and Methods:  REGARDS recruited 30,239 black and white U.S. participants aged ≥ 45 years between 2003 and 2007. FVIII and PC were measured in a case-cohort sample of 646 stroke, 654 CHD, and a 1,104-person random sample with follow-up for approximately 4.5 years. Hazard ratios (HRs) were estimated using Cox models adjusted for demographic and cardiovascular risk factors., Results:  Elevated FVIII (per standard deviation [SD] increase) was associated with increased risk of both stroke (HR, 1.26; 95% confidence interval [CI], 1.08, 1.46) and CHD (HR, 1.52; 95% CI, 1.29, 1.79), while there was no association of PC per SD decrease. For PC, there was a trend towards increased cardiovascular disease risk in the lowest values (bottom 5%). For stroke, there was no interaction between FVIII and low PC ( p interaction  = 0.55). For CHD, the adjusted HR of FVIII per SD increase was significantly greater with PC in the bottom 5% (HR, 3.59; 95% CI, 1.39, 8.29) than PC in the upper 95% (HR, 1.45; 95% CI, 1.23, 1.71; p interaction  = 0.07)., Conclusion:  Higher FVIII was associated with both CHD and stroke risk and the risk potentiated by low PC for CHD. Findings demonstrate that risks for cardiovascular diseases conferred by adverse levels of haemostasis biomarkers may be augmented by levels of other biomarkers., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Cardiovascular disease is a leading cause of death. Proneurotensin is a biomarker associated with the development of cardiovascular disease, cardiovascular mortality, and all-cause mortality. We assessed the association of fasting proneurotensin with mortal events by gender and race (black-white) in a US population. Using a case-cohort subpopulation of the Reasons for Geographic and Racial Differences in Stroke study, fasting proneurotensin was measured on a 1,046-person subcohort and in 651 participants with incident coronary heart disease. Higher proneurotensin was associated with all-cause mortality (hazard ratio [HR] 1.6 per interquartile range, 95% confidence interval [CI] 1.3 to 1.9) and cardiovascular mortality (HR 1.8, 95% CI 1.2 to 2.6). For all-cause and cardiovascular mortality, association was stronger in women (HR 1.9, 95% CI 1.4 to 2.6 and HR 2.5, 95% CI 1.4 to 4.7, respectively) than men (HR 1.4, 95% CI 1.0 to 1.8 and HR 1.4, 95% CI 0.9 to 2.3, respectively), although this difference was not significant. Proneurotensin predicted all-cause mortality in both races and was not predictive of cardiovascular mortality in whites but was in blacks. Proneurotensin was not associated with incident coronary heart disease events. Elevated proneurotensin levels predicted all-cause and cardiovascular mortality in both genders, with a trend toward stronger association in women. Associations were similar in blacks and whites. In conclusion, proneurotensin may be a useful biomarker for all-cause and cardiovascular mortality regardless of race, and it is potentially specific in women., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: This study examines the relationship between alcohol consumption and incident stroke among older adults and tests whether alcohol consumption contributes to observed race and sex differences in stroke., Method: Data are from a U.S. national cohort of black and white adults aged 45 and older, the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Current and past drinking levels were reported at baseline (2003-2007). Participants who had never had a stroke were followed for adjudicated stroke events through September 2015 (n = 27,265). We calculated Cox proportional hazard models for stroke, adjusting for demographic, socioeconomic, behavioral, and health characteristics., Results: Participants, mean age 64.7 years, consumed on average 2.2 drinks/week and experienced 1,140 first-time stroke events over median 9.1 years follow-up. Nondrinkers had a 12% higher risk of stroke than current drinkers; the risk of stroke among nondrinkers largely reflected high risks among past drinkers; these differences were explained by socioeconomic characteristics. Among current drinkers, light drinkers had significantly lower stroke risks than moderate drinkers after accounting for demographic, socioeconomic, behavioral, and health characteristics. Implications of alcohol did not differ between blacks and whites but did differ by sex: Especially among women, nondrinkers, and specifically past drinkers, had higher risks; these differences were largely explained by health characteristics and behaviors. Alcohol did not explain race and sex differences in stroke incidence., Discussion: Among older adults, those who used to, but no longer, drink had higher risks of stroke, especially among women; current light drinkers had the lowest risk of stroke.

Background and Purpose: Poststroke cognitive decline causes disability. Risk factors for poststroke cognitive decline independent of survivors' prestroke cognitive trajectories are uncertain., Methods: Among 22 875 participants aged ≥45 years without baseline cognitive impairment from the REGARDS cohort (Reasons for Geographic and Racial Differences in Stroke), enrolled from 2003 to 2007 and followed through September 2015, we measured the effect of incident stroke (n=694) on changes in cognitive functions and cognitive impairment (Six-Item Screener score <5) and tested whether patient factors modified the effect. Median follow-up was 8.2 years., Results: Incident stroke was associated with acute declines in global cognition, new learning, verbal memory, and executive function. Acute declines in global cognition after stroke were greater in survivors who were black ( P =0.04), men ( P =0.04), and had cardioembolic ( P =0.001) or large artery stroke ( P =0.001). Acute declines in executive function after stroke were greater in survivors who had

Competing Interests: The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.

Importance: Recent studies have suggested that the natriuretic peptide system may be endogenously suppressed in black individuals who are free of prevalent cardiovascular disease. Whether natriuretic peptide levels contribute to racial disparities in clinical outcomes is unknown., Objective: To examine racial differences in N-terminal pro-B-type natriuretic peptide (NTproBNP) levels and their association with all-cause mortality and cause-specific mortality in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study., Design, Setting, and Participants: Baseline NTproBNP levels were measured in a randomly selected sample of 4415 REGARDS study participants. Those with prevalent cardiovascular disease and renal dysfunction were excluded. From July 1, 2003, to September 12, 2007, among the remaining 1998 individuals, racial differences in NTproBNP levels were estimated, and the percentage difference in NTproBNP levels by race was meta-analyzed and compared with published results on participants free of prevalent cardiovascular disease from the Dallas Heart Study and Atherosclerosis Risk in Communities study, using random effects modeling. The association of NTproBNP levels, race, all-cause mortality, and cause-specific mortality in the REGARDS study was studied using appropriate modeling techniques. Data analysis was conducted from July 1, 2003, to March 31, 2016., Main Outcomes and Measures: Racial differences in NTproBNP levels and association with all-cause mortality and cause-specific mortality., Results: Among the 1998 participants studied (972 women and 1026 men; median age, 63 years [interquartile range, 54-72 years]), median NTproBNP levels in black individuals were significantly lower than those in white individuals (46 pg/mL [interquartile range, 23-91] vs 60 pg/mL [interquartile range, 33-106]; P < .001). With multivariable adjustment, NTproBNP levels were up to 27% lower in black individuals as compared with white individuals (β, -0.32; 95% CI, -0.40 to -0.24; P < .001) in the REGARDS study. In meta-analysis of the 3 cohorts, NTproBNP levels were 35% lower in black individuals than white individuals. Among the REGARDS study participants, for every 1-SD higher log NTproBNP, there was a 31% increased risk of death in the multivariable-adjusted model (hazard ratio, 1.31; 95% CI, 1.11-1.54). This increase was driven primarily by association of NTproBNP with cardiovascular mortality (hazard ratio, 1.69; 95% CI, 1.19-2.41). No interaction between race and NTproBNP levels was observed with all-cause mortality and cause-specific mortality., Conclusions and Relevance: Plasma NTproBNP levels are significantly lower in black individuals as compared with white individuals in the REGARDS study and in pooled results from the REGARDS study, Dallas Heart Study, and Atherosclerosis Risk in Communities study. Higher NTproBNP levels were associated with higher incidence of all-cause mortality and cardiovascular mortality in healthy black and white individuals, and this association did not differ by race.

Pathologic alterations in haemostasis cause bleeding disorders, but it is unknown if variation within the normal range relates to intracerebral haemorrhage (ICH) risk. It was our objective to assess the prospective associations of haemostasis biomarkers with ICH risk. The REasons for Geographic and Racial Differences in Stroke study (REGARDS) recruited 30,239 U. S. individuals aged ≥45 years. ICH was ascertained through biannual telephone contact and review of deaths followed by medical record evaluation. Haemostasis biomarkers (factor VIII (FVIII), factor IX (FIX), factor XI (FXI), fibrinogen, protein C, and D-dimer) were measured in a case cohort study consisting of ICH and a 1,104 person cohort random sample. The hazard ratio (HR) and 95 % confidence interval (CI) by biomarker were estimated using Cox models and adjusted for ICH risk factors. Individuals with a prior history of stroke, ICH or on warfarin were excluded. Over a median 5.8 years 66 ICH occurred. Fibrinogen, FVIII, FXI, and protein C were not associated with ICH risk in any analysis. Lower FIX increased risk of ICH with the bottom versus the top tertile of FIX associated with an HR of 5.68 (95 % CI 2.30, 14.05). D-dimer demonstrated a non-linear relationship with a potential threshold effect with increased risk only in the top 5th percentile (HR 3.22; 95 % CI 1.01, 10.31; p non-linear = 0.04).In conclusion, low FIX levels within the normal range were associated with increased ICH risk. These data suggest non-pathologic alterations in haemostasis impact intracranial bleeding risk.

Background: Stroke is a costly and debilitating disease that disproportionately affects blacks. Despite the efficacy of statins, evidence suggests racial disparities may exist in statin prescribing., Methods and Results: We analyzed discharge medications for participants hospitalized for an ischemic stroke during follow-up of the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study. Medications on admission and discharge were abstracted from medical records. Among the 666 eligible incident strokes (2003-2013), analyses were restricted to 323 participants who were not statin users at the time of admission and had no history of atrial fibrillation. Overall, 48.7% were prescribed a statin on discharge. In the Stroke Belt, participants aged 65 years and older were 47% less likely to be discharged on a statin compared with those younger than 65 years (relative risk [RR], 0.53; 95% CI, 0.38-0.74). This association was not observed in non-Stroke Belt residents. Outside the Stroke Belt, blacks were more likely than whites to be discharged on a statin (RR, 1.42; 95% CI, 1.04-1.94), while no black:white association was present among Stroke Belt residents (RR, 0.93; 95% CI, 0.69-1.26; P for interaction=0.228). Compared with women, men in the Stroke Belt were 31% less likely to be discharged on a statin (RR, 0.69; 95% CI, 0.50-0.94) while men outside the Stroke Belt were more likely to be discharged on a statin (RR, 1.38; 95% CI, 0.99-1.92; P for interaction=0.004)., Conclusions: Statin discharge prescribing may differ among Stroke Belt and non-Stroke Belt residents, particularly in older Americans and men., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background and Purpose: The standard for stroke risk stratification is the Framingham Stroke Risk Function (FSRF), an equation requiring an examination for blood pressure assessment, venipuncture for glucose assessment, and ECG to determine atrial fibrillation and heart disease. We assess a self-reported stroke risk function (SRSRF) to stratify stroke risk in comparison to the FSRF., Methods: Participants from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) were evaluated at baseline and followed for incident stroke. The FSRF was calculated using directly assessed stroke risk factors. The SRSRF was calculated from 13 self-reported questions to exclude those with prevalent stroke and assess stroke risk. Proportional hazards analysis was used to assess incident stroke risk using the FSRF and SRSRF., Results: Over an average 8.2-year follow-up, 939 of 23 983 participants had a stroke. The FSRF and SRSRF produced highly correlated risk scores ( r =0.852; 95% confidence interval, 0.849-0.856); however, the SRSRF had higher discrimination of stroke risk than the FSRF (c Spearman =0.852; 95% confidence interval, 0.849-0.856); however, the SRSRF had higher discrimination of stroke risk than the FSRF (c SRSRF =0.7266; 95% confidence interval, 0.7076-0.7457; c FSRF =0.0038). The 10-year stroke risk in the highest decile of predicted risk was 11.1% for the FSRF and 13.4% for the SRSRF.P =0.0038). The 10-year stroke risk in the highest decile of predicted risk was 11.1% for the FSRF and 13.4% for the SRSRF., Conclusions: A simple self-reported questionnaire can be used to identify those at high risk for stroke better than the gold standard FSRF. This instrument can be used clinically to easily identify individuals at high risk for stroke and also scientifically to identify a subpopulation enriched for stroke risk., (© 2017 American Heart Association, Inc.)

Background and Purpose: Stroke mortality is 30% higher in the rural United States. This could be because of either higher incidence or higher case fatality from stroke in rural areas., Methods: The urban-rural status of 23 280 stroke-free participants recruited between 2003 and 2007 in the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) was classified using the Rural-Urban Commuting Area scheme as residing in urban, large rural town/city, or small rural town or isolated areas. The risk of incident stroke was assessed using proportional hazards analysis, and case fatality (death within 30 days of stroke) was assessed using logistic regression. Models were adjusted for demographics, traditional stroke risk factors, and measures of socioeconomic status., Results: After adjustment for demographic factors and relative to urban areas, stroke incidence was 1.23-times higher (95% confidence intervals, 1.01-1.51) in large rural town/cities and 1.30-times higher (95% confidence intervals, 1.03-1.62) in small rural towns or isolated areas. Adjustment for risk factors and socioeconomic status only modestly attenuated this association, and the association became marginally nonsignificant ( P =0.071). There was no association of rural-urban status with case fatality ( P >0.47)., Conclusions: The higher stroke mortality in rural regions seemed to be attributable to higher stroke incidence rather than case fatality. A higher prevalence of risk factors and lower socioeconomic status only modestly contributed to the increased risk of incident stroke risk in rural areas. There was no evidence of higher case fatality in rural areas., (© 2017 American Heart Association, Inc.)

Estimated cardiorespiratory fitness (e-CRF) based on readily available clinical and self-reported data is a promising alternative to the costly traditional assessment of CRF using exercise equipment, but its role as a predictor for incident atrial fibrillation (AF) is unclear. This study included 10,126 participants (54.5% women, 35% African-American, mean age 63.2 years) from the Reasons for Geographic and Racial Differences in Stroke study who were free of AF at baseline. Baseline (2003 to 2007) e-CRF was determined using a previously validated nonexercise algorithm. Incident AF cases were identified at a follow-up examination by electrocardiogram and self-reported medical history of previous physician diagnosis. After a median follow-up of 9.4 years, 906 participants (8.9%) developed AF. In a multivariable logistic regression model adjusted for sociodemographics and baseline cardiovascular disease risk factors as well as incident coronary heart disease, heart failure, and stroke, each 1-metabolic equivalent of task increase in e-CRF was associated with a 5% lower risk of AF development (odds ratio [95% CI] 0.95 [0.92 to 0.99]; p = 0.0129). This association was stronger in women (OR [95% CI] 0.85 (0.79, 0.92) than in men (OR (95% CI) 0.88 (0.84, 0.93), interaction p value = 0.05. No significant interactions by age, race, history of cardiovascular disease, or physical limitations were observed. In conclusion, e-CRF using a nonexercise algorithm is a useful predictor of incident AF, which is consistent with previous reports using traditional CRF. This suggests that e-CRF using nonexercise algorithms may serve as a useful alternative to CRF measured by costly and time-consuming exercise testing., (Copyright © 2017 Elsevier Inc. All rights reserved.)

D-dimer, a biomarker of coagulation, is higher in blacks than in whites and has been associated with stroke and coronary heart disease (CHD). It was our objective to assess the association of higher D-dimer with stroke and CHD in blacks and whites. REGARDS recruited 30,239 black and white participants across the contiguous US and measured baseline D-dimer in stroke (n=646) and CHD (n=654) cases and a cohort random sample (n=1,104). Cox models adjusting for cardiovascular risk factors determined the hazard ratio (HR) for increasing D-dimer for cardiovascular disease with bootstrapping to assess the difference in HR for CHD versus stroke by race. D-dimer was higher with increasing age, female sex, diabetes, hypertension, pre-baseline cardiovascular disease and higher C-reactive protein (CRP). Accounting for cardiovascular risk factors, each doubling of D-dimer was associated with increased stroke (hazard ratio [HR] 1.15; 95 % confidence interval [CI] 1.01, 1.31) and CHD (HR 1.27; 95 % CI 1.11, 1.45) risk. The difference in the HR between CHD and stroke was 0.20 (95 % CI >0.00, 0.58) for blacks and 0.02 (95 % CI -0.30, 0.27) for whites. CRP mediated 22 % (95 % CI 5 %, 41 %) of the association between D-dimer and CHD and none of the association with stroke. Higher D-dimer increased the risk of stroke and CHD independent of cardiovascular risk factors and CRP, with perhaps a stronger association for CHD versus stroke in blacks than whites. These findings highlight potential different pathophysiology of vascular disease by disease site and race suggesting potential further studies targeting haemostasis in primary prevention of vascular disease.

Research on trace elements and the effects of their ingestion on human health is often seen in scientific literature. However, little research has been done on the distribution of trace elements in the environment and their impact on health. This paper examines what characteristics among participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study are associated with levels of environmental exposure to arsenic, magnesium, mercury, and selenium. Demographic information from REGARDS participants was combined with trace element concentration data from the US Geochemical Survey (USGS). Each trace element was characterized as either low (magnesium and selenium) or high (arsenic and mercury) exposure. Associations between demographic characteristics and trace element concentrations were analyzed with unadjusted and adjusted logistic regression models. Individuals who reside in the Stroke Belt have lower odds of high exposure (4th quartile) to arsenic (OR 0.33, CI 0.31, 0.35) and increased exposure to mercury (OR 0.65, CI 0.62, 0.70) than those living outside of these areas, while the odds of low exposure to trace element concentrations were increased for magnesium (OR 5.48, CI 5.05, 5.95) and selenium (OR 2.37, CI 2.22, 2.54). We found an association between levels of trace elements in the environment and geographic region of residence, among other factors. Future studies are needed to further examine this association and determine whether or not these differences may be related to geographic variation in disease.

Background: Moderate-to-severe kidney disease increases risk for sudden cardiac death (SCD). Limited studies have evaluated how mild degrees of kidney dysfunction impact SCD risk., Objective: The purpose of this study was to evaluate the association of albuminuria, which is one of the earliest biomarkers of kidney injury, and SCD., Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study is a prospective, population-based cohort of U.S. adults. Associations between albuminuria, which is categorized using urinary albumin-to-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and SCD were assessed independently and in combination., Results: After median follow-up of 6.1 years, we identified 335 SCD events. Compared to participants with ACR <15 mg/g, those with higher levels had an elevated adjusted risk of SCD (ACR 15-30 mg/g, hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.11-2.11; ACR >30 mg/g, HR 1.56, 95% CI 1.17-2.11). In contrast, compared to the group with eGFR >90 mL/min/1.73 m 2 , the adjusted risk of SCD was significantly elevated only among those with eGFR <45 mL/min/1.73 m 2 (HR 1.66, 95% CI 1.06-2.58). The subgroup with eGFR <45 mL/min/1.73 m 2 (n = 1003) comprised 3.7% of REGARDS, whereas ACR 15-30 mg/g (n = 3089 [11.3%]) and ACR >30 mg/g (n = 4040 [14.8%] were far more common. In the analysis that combined ACR and eGFR categories, albuminuria consistently identified individuals with eGFR ≥60 mLmin/1.73 m 2 who were at significantly increased SCD risk., Conclusion: Low levels of kidney injury as measured by ACR predict an increase in SCD risk., Competing Interests: None, (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)