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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. [ABSTRACT FROM AUTHOR]

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). 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. 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. 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. [ABSTRACT FROM AUTHOR]

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

Dietary and lifestyle evolutionary discordance is hypothesised to play a role in the aetiology of CVD, including CHD and stroke. We aimed to investigate associations of a previously reported, total (dietary plus lifestyle) evolutionary-concordance (EC) pattern score with incident CVD, CHD and stroke. We used multivariable Cox proportional hazards regression to investigate associations of the EC score with CVD, CHD and stroke incidence among USA Black and White men and women ≥45 years old in the prospective REasons for Geographic and Racial Differences in Stroke study (2003–2017). The EC score comprised seven equally weighted components: a previously reported dietary EC score (using Block 98 FFQ data) and six lifestyle characteristics (alcohol intake, physical activity, sedentary behaviour, waist circumference, smoking history and social network size). A higher score indicates a more evolutionary-concordant dietary/lifestyle pattern. Of the 15 467 participants in the analytic cohort without a CVD diagnosis at baseline, 1563 were diagnosed with CVD (967 with CHD and 596 with stroke) during follow-up (median 11·0 years). Among participants in the highest relative to the lowest EC score quintile, the multivariable-adjusted hazards ratios and their 95 % CI for CVD, CHD and stroke were, respectively, 0·73 (0·62, 0·86; P trend < 0·001), 0·72 (0·59, 0·89; P trend < 0·001) and 0·76 (0·59, 0·98; P trend = 0·01). The results were similar by sex and race. Our findings support that a more evolutionary-concordant diet and lifestyle pattern may be associated with lower risk of CVD, CHD and stroke. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Importance: A genetic variant in the TTR gene (rs76992529; Val122Ile), present more commonly in individuals with African ancestry (population frequency: 3%-4%), causes misfolding of the tetrameric transthyretin protein complex that accumulates as extracellular amyloid fibrils and results in hereditary transthyretin amyloidosis.Objective: To estimate the association of the amyloidogenic Val122Ile TTR variant with the risk of heart failure and mortality in a large, geographically diverse cohort of Black individuals.Design, Setting, and Participants: Retrospective population-based cohort study of 7514 self-identified Black individuals living in the US participating in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study with genetic data available and without heart failure at baseline. The participants were enrolled at the baseline visit (2003-2007). The end of follow-up for the majority of outcomes was on December 31, 2018. All-cause mortality data were available through December 31, 2020.Exposures: TTR Val122Ile (rs76992529) genotype.Main Outcome and Measures: The primary outcome was incident heart failure (first hospitalization for heart failure or death due to heart failure). The secondary outcomes were heart failure mortality, cardiovascular mortality, and all-cause mortality. The multivariable Cox proportional hazards regression analyses were adjusted for genetic ancestry and demographic, clinical, and social factors.Results: Among 7514 Black participants (median age, 64 years [IQR, 57-70 years]; 61% women), the population frequency of the TTR Val122Ile variant was 3.1% (232 variant carriers and 7282 noncarriers). During a median follow-up of 11.1 years (IQR, 5.9-13.5 years), incident heart failure occurred in 535 individuals (34 variant carriers and 501 noncarriers) and the incidence of heart failure was 15.64 per 1000 person-years among variant carriers vs 7.16 per 1000 person-years among noncarriers (adjusted hazard ratio [HR], 2.43 [95% CI, 1.71-3.46]; P < .001). Deaths due to heart failure occurred in 141 individuals (13 variant carriers and 128 noncarriers) and the incidence of heart failure mortality was 6.11 per 1000 person-years among variant carriers vs 1.85 per 1000 person-years among noncarriers (adjusted HR, 4.19 [95% CI, 2.33-7.54]; P < .001). Deaths due to cardiovascular causes occurred in 793 individuals (34 variant carriers and 759 noncarriers) and the incidence of cardiovascular death was 15.18 per 1000 person-years among variant carriers vs 10.61 per 1000 person-years among noncarriers (adjusted HR, 1.69 [95% CI, 1.19-2.39]; P = .003). Deaths due to any cause occurred in 2715 individuals (100 variant carriers and 2615 noncarriers) and the incidence of all-cause mortality was 41.46 per 1000 person-years among variant carriers vs 33.94 per 1000 person-years among noncarriers (adjusted HR, 1.46 [95% CI, 1.19-1.78]; P < .001). There was no significant interaction between TTR variant carrier status and sex on incident heart failure and the secondary outcomes.Conclusions and Relevance: Among a cohort of Black individuals living in the US, being a carrier of the TTR Val122Ile variant was significantly associated with an increased risk of heart failure. [ABSTRACT FROM AUTHOR]

Background Neurotensin, a neuropeptide with direct cardiac effects, has been associated with prospective risk of hypertension-related conditions through measurement of its precursor, pro-neurotensin/neuromedin N (pro-NT/NMN). Its association with incident hypertension has not been evaluated. Methods From 2003 to 2007, the REasons for Geographic And Racial Differences in Stroke (REGARDS) study enrolled 30,239 Black or White adults age ≥45. Pro-NT/NMN was measured in 1,692 participants without baseline hypertension (self-reported antihypertensive use or blood pressure ≥140/90 mm Hg) who underwent follow-up assessment in 2013–2016. A sensitivity analysis was conducted using a lower threshold (≥130/80 mm Hg) to define hypertension. Three robust Poisson regression models were fitted to risk of incident hypertension, adding demographics, cardiometabolic risk factors, and dietary covariates. Results Six hundred and fourteen participants developed hypertension over 9.4 years of follow-up. Pro-NT/NMN ranged from 14 to 1,246 pmol/l, with median [interquartile range] 154 [112, 206] pmol/l. Pro-NT/NMN was not associated with hypertension overall (fully adjusted incidence rate ratio per SD increment log pro-NT/NMN 1.03, 95% confidence interval 0.95–1.11). Results of sensitivity analysis did not differ substantially. Conclusions Baseline pro-NT/NMN was not associated with incident hypertension. This may be a result of neurotensin's long-term interactions with other molecular regulators of blood pressure, such as the renin–angiotensin–aldosterone system. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Low baseline plasma 25-hydroxyvitamin D (25(OH)D) is associated with increased risk of acute respiratory infections, but its association with long-term risk of sepsis remains unclear. Methods We performed a case-cohort analysis of participants selected from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a US cohort of 30239 adults aged ≥45 years. We measured baseline plasma 25(OH)D in 711 sepsis cases and in 992 participants randomly selected from the REGARDS cohort. We captured sepsis events by screening records with International Classification of Disease methods and then adjudicating clinical charts for significant, suspected infection and severe inflammatory response syndrome criteria on presentation. Results In the study sample, the median age of participants was 65.0 years, 41% self-identified as black, and 45% were male. Mean plasma 25(OH)D concentration was 25.8 ng/mL; for 31% of participants, it was <20 ng/mL. The adjusted risk of community-acquired sepsis was higher for each lower category of baseline 25(OH)D. Specifically, in a Cox proportional hazards model adjusting for multiple potential confounders, when compared to a baseline 25(OH)D >33.6 ng/mL, lower 25(OH)D groups were associated with higher hazards of sepsis (16.5–22.4 ng/mL; hazard ratio [HR]; 3.21; 95% confidence interval [CI], 1.98 to 5.21 and <16.5 ng/mL; HR, 6.81, 95% CI, 3.95 to 11.73). Results did not materially differ in analyses stratified by race or age. Conclusions In the REGARDS cohort of community-dwelling US adults, low plasma 25(OH)D measured at a time of relative health was independently associated with increased risk of sepsis. [ABSTRACT FROM AUTHOR]

Abstract Objective To investigate the association between biomarkers of inflammation and metabolic dysregulation and cancer mortality by obesity status. Methods Data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort was used to examine the associations between baseline biomarkers of inflammation (IL-6, IL-8, IL-10, and CRP) and metabolism (adiponectin, resisting and lipoprotein (a)) with cancer mortality among 1822 participants cancer-free at baseline. Weighted Cox proportional hazard regression with the robust sandwich method was used to estimate the hazard ratios and 95% confidence intervals (CIs) adjusting for baseline covariates and stratified by BMI (normal, overweight/obese) given the significant interaction between biomarkers and BMI (p < 0.1). Results During a mean follow-up of 8 years, there were statistically significant associations between cancer mortality and being in the highest vs. lowest tertile of IL-6 (HR: 5.3; 95% CI: 1.6, 17.8), CRP (HR: 3.4; 95% CI: 1.0, 11.2) and resistin (HR: 3.7; 95% CI: 1.2, 11.2) among participants with normal BMI. IL-6 was also associated with a 3-fold (HR: 3.5; 95% CI: 1.5, 8.1) increased risk of cancer mortality among participants with overweight/obesity; however, neither CRP nor resistin was significantly associated with cancer mortality in this group. Conclusions Higher baseline inflammatory and metabolic biomarkers were associated with significantly increased risk of cancer mortality after adjusting for baseline risk factors and the associations varied by BMI. Cancer patients may benefit from interventions that modulate inflammatory and metabolic biomarkers. [ABSTRACT FROM AUTHOR]

Little is known concerning the type of activity that should be substituted for sedentary time and its potentially most hazardous form (prolonged sedentary bouts) to impart health benefit. We used isotemporal substitution techniques to examine whether 1) replacing total sedentary time with light-intensity or moderate to vigorous physical activity (LIPA or MVPA) or 2) replacing prolonged sedentary bouts with shorter sedentary bouts is associated with reductions in all-cause mortality risk. Participants (n = 7,999) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national cohort of US adults aged ≥45 years, were studied. Sedentary time was measured by accelerometry between 2009 and 2013. There was a beneficial association with mortality risk for replacing total sedentary time with both LIPA (per 30 minutes, hazard ratio (HR) = 0.83; 95% confidence interval (CI): 0.80, 0.87) and MVPA (per 30 minutes, HR = 0.65; 95% CI: 0.50, 0.85). Similarly, there was a beneficial association for replacing prolonged sedentary-bout time with LIPA and MVPA but not for replacement with shorter sedentary bouts (per 30 minutes, HR = 1.00; 95% CI: 0.96, 1.03). These findings suggest short sedentary bouts still carry mortality risk and are not a healthful alternative to prolonged sedentary bouts. Instead, physical activity of any intensity is needed to mitigate the mortality risks incurred by sedentary time. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Importance: The high prevalence of hypertension among the US black population is a major contributor to disparities in life expectancy; however, the causes for higher incidence of hypertension among black adults are unknown.Objective: To evaluate potential factors associated with higher risk of incident hypertension among black adults.Design, Setting, and Participants: Prospective cohort study of black and white adults selected from a longitudinal cohort study of 30 239 participants as not having hypertension at baseline (2003-2007) and participating in a follow-up visit 9.4 years (median) later.Exposures: There were 12 clinical and social factors, including score for the Southern diet (range, -4.5 to 8.2; higher values reflect higher level of adherence to the dietary pattern), including higher fried and related food intake.Main Outcomes and Measures: Incident hypertension (systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or use of antihypertensive medications) at the follow-up visit.Results: Of 6897 participants (mean [SD] age, 62 [8] years; 26% were black adults; and 55% were women), 46% of black participants and 33% of white participants developed hypertension. Black men had an adjusted mean Southern diet score of 0.81 (95% CI, 0.72 to 0.90); white men, -0.26 (95% CI, -0.31 to -0.21); black women, 0.27 (95% CI, 0.20 to 0.33); and white women, -0.57 (95% CI, -0.61 to -0.54). The Southern diet score was significantly associated with incident hypertension for men (odds ratio [OR], 1.16 per 1 SD [95% CI, 1.06 to 1.27]; incidence of 32.4% at the 25th percentile and 36.1% at the 75th percentile; difference, 3.7% [95% CI, 1.4% to 6.2%]) and women (OR, 1.17 per 1 SD [95% CI, 1.08 to 1.28]; incidence of 31.0% at the 25th percentile and 34.8% at the 75th percentile; difference, 3.8% [95% CI, 1.5% to 5.8%]). The Southern dietary pattern was the largest mediating factor for differences in the incidence of hypertension, accounting for 51.6% (95% CI, 18.8% to 84.4%) of the excess risk among black men and 29.2% (95% CI, 13.4% to 44.9%) of the excess risk among black women. Among black men, a higher dietary ratio of sodium to potassium and an education level of high school graduate or less each mediated 12.3% of the excess risk of incident hypertension. Among black women, higher body mass index mediated 18.3% of the excess risk; a larger waist, 15.2%; less adherence to the Dietary Approaches to Stop Hypertension diet, 11.2%; income level of $35 000 or less, 9.3%; higher dietary ratio of sodium to potassium, 6.8%; and an education level of high school graduate or less, 4.1%.Conclusions and Relevance: In a mediation analysis comparing incident hypertension among black adults vs white adults in the United States, key factors statistically mediating the racial difference for both men and women included Southern diet score, dietary ratio of sodium to potassium, and education level. Among women, waist circumference and body mass index also were key factors. [ABSTRACT FROM AUTHOR]

Background. Prior studies suggest disparities in sepsis risk and outcomes based on place of residence. We sought to examine the association between neighborhood socioeconomic status (nSES) and hospitalization for infection and sepsis. Methods. We conducted a prospective cohort study using data from 30 239 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. nSES was defined using a score derived from census data and classified into quartiles. Infection and sepsis hospitalizations were identified over the period 2003-2012. We fit Cox proportional hazards models, reporting hazard ratios (HRs) with 95% confidence intervals (CIs) and examining mediation by participant characteristics. Results. Over a median follow-up of 6.5 years, there were 3054 hospitalizations for serious infection. Infection incidence was lower for participants in the highest nSES quartile compared with the lowest quartile (11.7 vs 15.6 per 1000 person-years). After adjustment for demographics, comorbidities, and functional status, infection hazards were also lower for the highest quartile (HR, 0.84 [95% CI, .73-.97]), with a linear trend (P = .011). However, there was no association between nSES and sepsis at presentation among those hospitalized with infection. Physical weakness, income, and diabetes had modest mediating effects on the association of nSES with infection. Conclusions. Our study shows that differential infection risk may explain nSES disparities in sepsis incidence, as higher nSES is associated with lower infection hospitalization rates, but there is no association with sepsis among those hospitalized. Mediation analysis showed that nSES may influence infection hospitalization risk at least partially through physical weakness, individual income, and comorbid diabetes. [ABSTRACT FROM AUTHOR]

Objective: This study examined whether metabolic health status is associated with risk of cancer mortality and whether this varies by body mass index (BMI) category.Methods: A prospective study of 22,514 participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort was performed. Metabolically unhealthy status was defined as having three or more of the following: (1) elevated fasting glucose, (2) high triglycerides, (3) dyslipidemia, (4) hypertension, and (5) elevated waist circumference. Participants were categorized into normal weight (BMI 18.5-24.9 kg/m2 ), overweight (BMI 25.0-29.9 kg/m2 ), and obesity (BMI ≥ 30 kg/m2 ) groups. Cox proportional hazards regression was performed to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) for cancer mortality during follow-up.Results: Among participants with normal weight, participants who were metabolically unhealthy had an increased risk of cancer mortality (HR: 1.65; 95% CI: 1.20-2.26) compared with metabolically healthy participants. The overall mortality risk for participants who were metabolically unhealthy and had normal weight was stronger for obesity-related cancers (HR: 2.40; 95% CI: 1.17-4.91). Compared with participants with normal weight, those who were metabolically healthy and overweight were at a reduced risk of any cancer mortality (adjusted HR: 0.79; 95% CI: 0.63-0.99).Conclusions: There was an increased risk of overall and obesity-related cancer mortality among metabolically unhealthy participants with normal weight. [ABSTRACT FROM AUTHOR]

Associations of calcium and dairy product intakes with cardiovascular disease risk and cancer mortality are controversial. We investigated associations of calcium and dairy product intakes with mortality in the prospective REasons for Geographic and Racial Differences in Stroke study (n = 30,239). Of 2,966 total deaths, 32.3% were from CVD and 28.8% from cancer. For those in the upper relative to the lowest quintile of intakes, from Cox proportional hazards regression models, the multivariable-adjusted hazard ratios (HRs) for all-cause mortality were 1.13 (95% confidence intervals [CI] 0.95–1.35; P-trend 0.004) for whole milk, and 0.75 (CI 0.61–0.93; P-trend 0.001) for nonfat milk; for CVD mortality the corresponding HRs were 0.80 (CI 0.55–1.16; P-trend 0.80) and 0.72 (CI 0.49–1.05; P-trend 0.06); and for cancer mortality they were 1.56 (CI 1.17–2.08; P-trend 0.006) and 0.89 (CI 0.62–1.28; P-trend 0.86). Calcium (total, dietary, supplemental) and total dairy product intakes were not associated with all-cause, cardiovascular, or cancer mortality. These results suggest that whole milk consumption may be directly associated with cancer mortality; non-fat milk consumption may be inversely associated with all-cause and cardiovascular- and cancer-specific mortality; and calcium intake independent of milk product intakes may not be associated with mortality. [ABSTRACT FROM AUTHOR]

Background: Flavonoids may have beneficial cerebrovascular effects, but evidence from racially and geographically representative cohorts in comprehensive flavonoid databases is lacking. Given racial and geographic disparities in stroke incidence, representative cohort studies are needed.Objectives: We evaluated the association between flavonoid intake and incident ischemic stroke in a biracial, national cohort using updated flavonoid composition tables and assessed differences in flavonoid intake by sex, race, and region of residence.Methods: We evaluated 20,024 participants in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study, a biracial prospective study. Participants with stroke history or missing dietary data were excluded. Flavonoid intake was estimated by using a Block98 food frequency questionnaire and the USDA's Provisional Flavonoid Addendum and Proanthocyanidin Database. Associations between quintiles of flavonoid intake and incident ischemic stroke were evaluated by using Cox proportional hazards models, adjusting for confounders.Results: Over 6.5 y, 524 acute ischemic strokes occurred. Flavanone intake was lower in the Southeastern United States but higher in blacks than in whites. After multivariable adjustment, flavanone intake was inversely associated with incident ischemic stroke (HR: 0.72; 95% CI: 0.55, 0.95; P-trend = 0.03). Consumption of citrus fruits and juices was inversely associated with incident ischemic stroke (HR: 0.69; 95% CI: 0.53, 0.91; P-trend = 0.02). Total flavonoids and other flavonoid subclasses were not associated with incident ischemic stroke. There was no statistical interaction with sex, race, or region for any flavonoid measure.Conclusions: Greater consumption of flavanones, but not total or other flavonoid subclasses, was inversely associated with incident ischemic stroke. Associations did not differ by sex, race, or region for the association; however, regional differences in flavanone intake may contribute to regional disparities in ischemic stroke incidence. Higher flavanone intake in blacks suggests that flavanone intake is not implicated in racial disparities in ischemic stroke incidence. [ABSTRACT FROM AUTHOR]

Background: Flavonoids are dietary polyphenolic compounds with a variety of proposed beneficial cardiovascular effects, but rigorous prospective studies that examine the association between flavonoid intake and incident coronary heart disease (CHD) in geographically and racially diverse US samples are limited. Objective: With the use of the new, expanded USDA flavonoid database, we assessed the association between total flavonoid and flavonoid subclass intakes with incident CHD in a biracial and geographically diverse cohort, as well as effect modification by age, sex, race, and region of residence. Design: Participants were 16,678 black and white men and women enrolled in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study, a national prospective cohort study. All participants were without CHD at baseline, and all completed a Block98 food-frequency questionnaire. Flavonoid intakes were estimated from USDA flavonoid databases, which were recently improved to address missing values for cooked foods and to adjust for flavonoid losses due to processing. Incident CHD events were participant reported and adjudicated by experts. Quintiles of flavonoid intake were examined as predictors of incident CHD by using Cox proportional hazards regression to obtain HRs. Tests for trend used the quintile medians. Results: Over a mean ± SD follow-up of 6.0 ± 1.9 y, 589 CHD events occurred. High flavonoid intake was associated with selfidentified white race, exercise, not smoking, more education, and higher income. In models that adjusted for sociodemographic, health behavior, and dietary factors, there was an inverse association between anthocyanidin and proanthocyanidin intakes and incident CHD (HRs for quintile 5 compared with quintile 1--anthocyanidins: 0.71; 95% CI: 0.52, 0.98; P-trend = 0.04; proanthocyanidins: 0.63; 95% CI: 0.47, 0.84; P-trend = 0.02). There was no association between total flavonoid or other flavonoid subclass intakes and incident CHD. Conclusions: Reported anthocyanidin and proanthocyanidin intakes were inversely associated with incident CHD. There was no significant effect modification by age, sex, race, or region of residence. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of comorbid depressive symptoms and/or stress on adverse cardiovascular (CV) outcomes in individuals with diabetes compared with those without diabetes.Research Design and Methods: Investigators examined the relationship between baseline depressive symptoms and/or stress in adults with and without diabetes and physician-adjudicated incident CV outcomes including stroke, myocardial infarction/acute coronary heart disease, and CV death over a median follow-up of 5.95 years in the national REGARDS cohort study.Results: Subjects included 22,003 adults (4,090 with diabetes) (mean age 64 years, 58% female, 42% black, and 56% living in the southeastern "Stroke Belt"). Elevated stress and/or depressive symptoms were more common in subjects with diabetes (36.8% vs. 29.5%; P < 0.001). In fully adjusted models, reporting either elevated stress or depressive symptoms was associated with a significantly increased incidence of stroke (HR 1.57 [95% CI 1.05, 2.33] vs. 1.01 [0.79, 1.30]) and CV death (1.53 [1.08, 2.17] vs. 1.12 [0.90, 1.38]) in subjects with diabetes but not in those without diabetes. The combination of both elevated stress and depressive symptoms in subjects with diabetes was associated with a higher incidence of CV death (2.15 [1.33, 3.47]) than either behavioral comorbidity alone (1.53 [1.08, 2.17]) and higher than in those with both elevated stress and depressive symptoms but without diabetes (1.27 [0.86, 1.88]).Conclusions: Comorbid stress and/or depressive symptoms are common in individuals with diabetes and together are associated with progressively increased risks for adverse CV outcomes. [ABSTRACT FROM AUTHOR]

Background: We investigated the association between income-education groups and incident coronary heart disease (CHD) in a national prospective cohort study.Methods: The REasons for Geographic And Racial Differences in Stroke study recruited 30,239 black and white community-dwelling adults between 2003 and 2007 and collected participant-reported and in-home physiologic variables at baseline, with expert adjudicated CHD endpoints during follow-up. Mutually exclusive income-education groups were: low income (annual household income <$35,000)/low education (< high school), low income/high education, high income/low education, and high income/high education. Cox models estimated hazard ratios (HR) for incident CHD for each exposure group, examining differences by age group.Results: At baseline, 24,461 participants free of CHD experienced 809 incident CHD events through December 31, 2011 (median follow-up 6.0 years; interquartile range 4.5-7.3 years). Those with low income/low education had the highest incidence of CHD (10.1 [95% CI 8.4-12.1]/1000 person-years). After full adjustment, those with low income/low education had higher risk of incident CHD (HR 1.42 [95% CI: 1.14-1.76]) than those with high income/high education, but findings varied by age. Among those aged <65 years, compared with those reporting high income/high education, risk of incident CHD was significantly higher for those reporting low income/low education and low income/high education (adjusted HR 2.07 [95% CI 1.42-3.01] and 1.69 [95% CI 1.30-2.20], respectively). Those aged ≥ 65 years, risk of incident CHD was similar across income-education groups after full adjustment.Conclusion: For younger individuals, low income, regardless of education, was associated with higher risk of CHD, but not observed for ≥ 65 years. Findings suggest that for younger participants, education attainment may not overcome the disadvantage conferred by low income in terms of CHD risk, whereas among those ≥ 65 years, the independent effects of income and education are less pronounced. [ABSTRACT FROM AUTHOR]

Background: The oxidative balance score (OBS) is a composite estimate of the overall pro- and antioxidant exposure status in an individual. The aim of this study was to determine the association between OBS and renal disease.Methods: Using the Reasons for Geographic and Racial Differences in Stroke cohort study, OBS was calculated by combining 13 a priori-defined pro- and antioxidant factors by using baseline dietary and lifestyle assessment. OBS was divided into quartiles (Q1-Q4) with the lowest quartile, Q1 (predominance of pro-oxidants), as the reference. Multivariable logistic regression and Cox proportional hazards models were used to estimate adjusted ORs for albuminuria defined as urine albumin/creatinine ratio (ACR)>30 mg/g, macroalbuminuria defined as ACR>300 mg/g and chronic kidney disease (CKD) defined as estimated glomerular filtration rate<60 ml/min/1.73 m2 according to the Chronic Kidney Disease Epidemiology Collaboration and hazards ratios for end-stage renal disease (ESRD), respectively.Results: Of the 19,461 participants analyzed, 12.9% had albuminuria and 10.1% had CKD at baseline; over a median follow-up of 3.5 years (range 2.14-4.32 years), 0.46% developed ESRD. Higher OBS quartiles were associated with lower prevalence of CKD (OR vs. Q1: Q2=0.93 [95% CI 0.80-1.08]; Q3=0.90 [95% CI 0.77-1.04] and Q4=0.79 [95% CI 0.67-0.92], p for trend<.01). The associations between OBS and albuminuria (p for trend 0.31) and incident ESRD (p for trend 0.56) were not significant in the fully adjusted models.Conclusions: These findings suggest that higher OBS is associated with lower prevalence of CKD. Lack of association with ESRD incidence in the multivariable analyses indicates that temporal relation between OBS and renal damage remains unclear. [ABSTRACT FROM AUTHOR]

Objective: High dietary glycemic load (GL) has been associated with an increased risk for chronic diseases, including type 2 diabetes, coronary heart disease, and selected cancers. The aim of this study was to identify the main food and food group contributors to dietary GL in a representative sample of US adults to inform future interventions. Methods: Participants were from the REGARDS (REasons for Geographic and Racial Differences in Stroke) study, a longitudinal cohort of 30 239 community-dwelling black and white women and men ages >45 y from throughout the United States. Diet was assessed with a food frequency questionnaire. The amount of each carbohydrate food, and its glycemic index, were used to calculate GL values for each carbohydrate food reported. These were totaled to estimate the mean total daily GL for each participant. Individual carbohydrate foods also were collapsed into 18 carbohydrate food groups, and the portion of the total GL contributed by each carbohydrate food and food group was determined. Analyses were conducted overall, by race/sex groups, and by region. Results: Sweetened beverages were the main contributors to GL overall (12.14 median percentage [median %] of daily GL), by far the largest contributors in black men (17.79 median %) and black women (16.43 median %), and major contributors in white men (12.02 median %) and white women (11.22 median %). Other important contributors to GL overall and in all race/sex groups and regions included breads, starchy side dishes, and cereals. Conclusions: In this US cohort of white and black adults, sweetened beverages were major contributors to GL overall, especially in black participants. This information may help to inform future interventions targeting reduction in dietary GL. [ABSTRACT FROM AUTHOR]

Background: Whether elevated intakes of trans fatty acids (TFAs) increase the risk of stroke remains unclear. Except for the Women's Health Initiative-Observational Study, most studies that directly assessed the association between TFA intake and stroke yielded null results. Objective: The aim of this study was to investigate the association between TFA intake and stroke incidence. Design: We prospectively investigated the association between TFA intake and stroke incidence in black and white men and women (n = 17,107) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. Participants were recruited between 2003 and 2007 from the continental United States and followed for incident stroke. Diet was assessed by using the Block 1998 food-frequency questionnaire. Cox regression was used to test whether energy-adjusted TFA intake in 1-SD increments was associated with incident stroke. Results: During a median follow-up of 7 y, 479 strokes were identified, including 401 ischemic strokes. Sex modified the association between TFA intake and stroke (P-interaction = 0.06), and thus the results were stratified by sex. In fully adjusted models, a 1-SD (2-g/d) increase in TFA intake was associated with an increased risk of any stroke in men (HR: 1.14; 95% CI: 1.02, 1.28) but not in women (HR: 0.93; 95% CI: 0.79, 1.11). Similarly, our results showed an increased risk of ischemic stroke in men (HR: 1.13; 95% CI: 1.00, 1.28) but not in women (HR: 0.93; 95% CI: 0.77, 1.12). Conclusions: We show that sex modifies the association between TFA intake and stroke; for every 2-g/d increase in TFA intake, there was a 14% increase in the risk of stroke in men but not in women. Our findings provide further evidence to support the concerted effort to minimize TFAs in the diet. [ABSTRACT FROM AUTHOR]

Background: The United States implemented mandatory folic acid fortification of enriched cereal grains in 1998. Although several studies have documented the resulting decrease in anemia and folate deficiency, to our knowledge, no one has determined the prevalence of folate-deficiency anemia after fortification. Objective: We determined the prevalence of folate deficiency and folate-deficiency anemia within a sample of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Design: The REGARDS cohort is a prospective cohort of 30,239 black and white participants living in the contiguous United States. We measured serum folate concentrations in a random sample of 1546 REGARDS participants aged ≥50 y with baseline hemoglobin and red blood cell mean corpuscular volume measurements. Folate deficiency was defined as a serum folate concentration < 6.6 nmol/L (<3.0 ng/mL), and anemia was defined as a hemoglobin concentration,13 g/dL in men and <12 g/dL in nonpregnant women (WHO criteria). Folate-deiciency anemia was defined as the presence of both folate deficiency and anemia. Results: The mean hemoglobin concentration was 13.6 g/dL, and 15.9% of subjects had anemia. The median serum folate concentration was 34.2 nmol/L (15.1 ng/mL), and only 2 of 1546 participants 0.1%) were folate deficient. Both subjects were African American women with markedly elevated C-reactive protein concentrations, macrocytosis, and normal serum cobalamin concentrations; only one subject was anemic. Overall, the prevalence of folate-deficiency anemia was <0.1% (1 of 1546 subjects). Conclusion: Our data suggest that, after mandatory folic acid fortification, the prevalence of folate-deficiency anemia is nearly nonexistent in a community-dwelling population in the United States. [ABSTRACT FROM AUTHOR]

Background: A high intake of trans fatty acids decreases HDL cholesterol and is associated with increased LDL cholesterol, inflammation, diabetes, cancer, and mortality from cardiovascular disease. The relation between trans fat intake and all-cause mortality has not been established. Objective: The aim of this study was to determine the relation between trans fat intake and all-cause mortality. Design: We used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study--a prospective cohort study of white and black men and women residing in the continental United States. Energy-adjusted trans fat intake was categorized into quintiles, and Cox-regression was used to evaluate the association between trans fat intake and all-cause mortality. Results: During 7 y of follow-up, there were 1572 deaths in 18,513 participants included in REGARDS. From the first to the fifth quintile of trans fat intake, the mortality rates per 1000 person-years of follow-up (95% CIs) were 12.8 (11.3, 14.5), 14.3 (12.7, 16.2), 14.6 (13.0, 16.5), 19.0 (17.1, 21.1), and 23.6 (21.5, 25.9), respectively. After adjustment for demographic factors, education, and risk factors for mortality, the HRs (95% CIs) for all-cause mortality were 1.00, 1.03 (0.86, 1.23), 0.98 (0.82, 1.17), 1.25 (1.05, 1.48), and 1.24 (1.05, 1.48), respectively (P-trend = 0.004). The population attributable risk due to trans fat intake was 7% (95% CI: 5%, 8%). Conclusion: Higher trans fat intake is associated with an increased risk of all-cause mortality. [ABSTRACT FROM AUTHOR]

Longitudinal cohort studies normally identify and adjudicate incident events detected during follow-up by retrieving medical records. There are several reasons why the adjudication process may not be successfully completed for a suspected event including the inability to retrieve medical records from hospitals and an insufficient time between the suspected event and data analysis. These “incomplete adjudications” are normally assumed not to be events, an approach which may be associated with loss of precision and introduction of bias. In this article, the authors evaluate the use of multiple imputation methods designed to include incomplete adjudications in analysis. Using data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, 2008−2009, they demonstrate that this approach may increase precision and reduce bias in estimates of the relations between risk factors and incident events. [ABSTRACT FROM PUBLISHER]

Inflammation biomarkers, including higher high-sensitivity C-reactive protein (hsCRP) levels, higher white blood cell (WBC) counts, and lower serum albumin levels, are associated with an increased risk of all-cause mortality. Many studies have examined these biomarkers individually, but less is known about their joint association with mortality. hsCRP, WBC count, and serum albumin were measured at baseline in the Reasons for Geographic and Racial Differences in Stroke Study cohort members, who were enrolled in 2003–2007. Over 4.5 years, there were 1,062 deaths in 17,845 participants. High-risk categories were defined as hsCRP or WBC levels above the 75th percentile (5.1 mg/L and 6.9 × 109 cells/L, respectively) and albumin levels below the 25th percentile (4.00 g/dL). The authors derived 4 groups that corresponded to 0 (n = 8,341), 1 (n = 6,277), 2 (n = 2,635), or 3 (n = 592) biomarkers in the high-risk category. After adjustment for age, sex, waist circumference, race, region, smoking, alcohol use, income, educational level, physical activity frequency, and medical history and compared with those with no biomarkers in the high-risk category, the hazard ratios for all-cause mortality for 1, 2, and 3 biomarkers in the high-risk category were 1.56 (95% confidence interval: 1.33, 1.82), 2.19 (95% confidence interval: 1.84, 2.62), and 2.96 (95% confidence interval: 2.30, 3.80), respectively (Ptrend < 0.0001). Adding the 3 inflammation biomarkers to a fully adjusted model improved risk discrimination by 23.7% (95% confidence interval: 9.3, 39.9). Measurement of more than 1 biomarker is more useful in risk prediction than single biomarkers. [ABSTRACT FROM AUTHOR]

Purpose: To examine the hypothesis that longer distance from home-to-hospital is associated with worse outcomes among hospitalizations for community-acquired sepsis.Methods: A secondary analysis of data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) prospective cohort of 30,239 white and Black US adults greater than or equal to 45 years old was conducted. Self-reported hospitalizations for serious infection between 2003 and 2012 fulfilling 2/4 systemic inflammatory response syndrome criteria were included. Estimated driving distance was derived from geocoded data and evaluated continuously and as quartiles of very close, close, far, very far (<3.1, 3.1-5.8, 5.9-11.5, and >11.5 miles respectively). The primary outcome was 30-day mortality while the secondary outcome was sequential organ failure assessment (SOFA) score on arrival.Results: Of the 912 hospitalizations for community-acquired sepsis had adequate data for analysis. The median (interquartile range) estimated driving distance was 5.8 miles (3.1,11.7), and 54 (5.9%) experienced the primary outcome. Compared to living very close, participants living very far had a mortality odds ratio of 1.30 (95% CI 0.64,2.62) and presenting SOFA score difference of 0.33 (95% CI -0.03,0.68).Conclusions: Among a national sample of community-acquired sepsis hospitalizations, there was no significant association between home-to-hospital distance and either 30-day mortality or SOFA score on hospital presentation. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to explore the relationship between TV/video viewing, as a measure of sedentary behavior, and risk of incident stroke in a large prospective cohort of men and women.Methods: This analysis involved 22,257 participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who reported at baseline the amount of time spent watching TV/video daily. Suspected stroke events were identified at six-monthly telephone calls and were physician-adjudicated. Cox proportional hazards models were used to examine risk of stroke at follow-up.Results: During 7.1years of follow-up, 727 incident strokes occurred. After adjusting for demographic factors, watching TV/video ≥4h/day (30% of the sample) was associated with a hazard ratio of 1.37 increased risk of all stroke (95% confidence interval (CI), 1.10-1.71) and incident ischemic stroke (hazard ratio 1.35, CI 1.06-1.72). This association was attenuated by socioeconomic factors such as employment status, education and income.Conclusions: These results suggest that while TV/video viewing is associated with increased stroke risk, the effect of TV/video viewing on stroke risk may be explained through other risk factors. [ABSTRACT FROM AUTHOR]

Objectives: Cognitive impairment is an important consequence of sepsis. We sought to determine long-term trajectories of cognitive function after sepsis.Design: Prospective study of the Reasons for Geographic and Racial Differences in Stroke cohort.Setting: United States.Patients: Twenty-one thousand eight-hundred twenty-three participants greater than or equal to 45 years, mean (sd) age 64.3 (9.2) years at first cognitive assessment, 30.9% men, and 27.1% Black.Measurements and Main Results: The main exposure was time-dependent sepsis hospitalization. The primary outcome was global cognitive function (Six-Item Screener range, 0-6). Secondary outcomes were incident cognitive impairment (Six-Item Screener score ≤ 4 [impaired] vs ≥5 [unimpaired]), new learning (Consortium to Establish a Registry for Alzheimer Disease Word List Learning range, 0-30), verbal memory (word list delayed recall range, 0-10), and executive function/semantic fluency (animal fluency test range, ≥ 30). Over a median follow-up of 10 years (interquartile range, 6-12 yr), 840 (3.8%) experienced sepsis (incidence 282 per 1,000 person-years). Sepsis was associated with faster long-term declines in Six-Item Screener (-0.02 points per year faster [95% CI, -0.01 to -0.03]; p < 0.001) and faster long-term rates of incident cognitive impairment (odds ratio 1.08 per year [95% CI, 1.02-1.15]; p = 0.008) compared with presepsis slopes. Although cognitive function acutely changed after sepsis (0.05 points [95% CI, 0.01-0.09]; p = 0.01), the odds of acute cognitive impairment (Six-Item Screener ≤ 4) immediately after sepsis was not significant (odds ratio, 0.81 [95% CI, 0.63-1.06]; p = 0.12). Sepsis hospitalization was not associated with acute changes or faster declines in word list learning, word list delayed recall, or animal fluency test.Conclusions: Sepsis is associated with accelerated long-term decline in global cognitive function. [ABSTRACT FROM AUTHOR]