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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.

Purpose: Relative to White adults, Black adults have a substantially higher prevalence of hypertension and diabetes, both key risk factors for stroke, cardiovascular disease, cognitive impairment, and dementia. Blood biomarkers have shown promise in identifying contributors to racial disparities in many chronic diseases., Methods: We outline the study design and related statistical considerations for a nested cohort study, the Biomarker Mediators of Racial Disparities in Risk Factors (BioMedioR) study, within the 30,239-person biracial REasons for Geographic And Racial Differences in Stroke (REGARDS) study (2003-present). Selected biomarkers will be assessed for contributions to racial disparities in risk factor development over median 9.4 years of follow-up, with initial focus on hypertension, and diabetes. Here we outline study design decisions and statistical considerations for the sampling of 4,400 BioMedioR participants., Results: The population for biomarker assessment was selected using a random sample study design balanced across race and sex to provide the optimal opportunity to describe association of biomarkers with the development of hypertension and diabetes. Descriptive characteristics of the BioMedioR sample and analytic plans are provided for this nested cohort study., Conclusions: This nested biomarker study will examine pathways with the target to help explain racial differences in hypertension and diabetes incidence., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: More inflammation is associated with greater risk incident hypertension, and Black United States (US) adults have excess burden of hypertension. We investigated whether increased inflammation as quantified by higher C-reactive protein (CRP) explains the excess incidence in hypertension experienced by Black US adults., Methods: We included 6,548 Black and White REasons for Geographic and Racial Differences in Stroke (REGARDS) participants without hypertension at baseline (2003-2007) who attended a second visit (2013-2016). Sex-stratified risk ratios (RRs) for incident hypertension at the second exam in Black compared to White individuals were estimated using Poisson regression adjusted for groups of factors known to partially explain the Black-White differences in incident hypertension. We calculated the percent mediation by CRP of the racial difference in hypertension., Results: Baseline CRP was higher in Black participants. The Black-White RR for incident hypertension in the minimally adjusted model was 1.33 (95% confidence interval 1.22, 1.44) for males and 1.15 (1.04, 1.27) for females. CRP mediated 6.6% (95% confidence interval 2.7, 11.3%) of this association in females and 19.7% (9.8, 33.2%) in males. In females, CRP no longer mediated the Black-White RR in a model including waist circumference and body mass index, while in males the Black-White difference was fully attenuated in models including income, education and dietary patterns., Conclusions: Elevated CRP attenuated a portion of the unadjusted excess risk of hypertension in Black adults, but this excess risk was attenuated when controlling for measures of obesity in females and diet and socioeconomic factors in males. Inflammation related to these risk factors might explain part of the Black-White disparity in hypertension., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Low circulating 25-hydroxyvitamin D (25[OH]D) has been associated with increased risk of coronary heart disease (CHD), but whether this association differs by race is unclear., Methods: We examined the association of 25[OH]D with incident CHD in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a prospective cohort study of black and white adults ≥45 years of age enrolled between 2003 and 2007 with follow-up through December 31, 2011. Using a case-cohort design, we measured 25[OH]D in 829 participants who developed incident CHD (cases) and in 813 participants without CHD randomly selected from the REGARDS cohort (comparison subcohort). Cox proportional hazards models were used to examine associations of 25[OH]D with incident CHD adjusting for established CHD risk factors in the study sample overall and stratified by race., Results: In the fully adjusted model, lower quintiles of 25[OH]D were associated with a greater risk of incident CHD (25[OH]D > 33.6 ng/mL reference; 25[OH]D > 27.1-33.6 ng/mL, hazard ratio [HR] 2.79, 95% CI 1.64-4.76; 25[OH]D > 22.4-27.1 ng/mL, HR 2.77, 95% CI 1.57-4.89; 25[OH]D > 16.5-22.4 ng/mL, HR 5.52, 95% CI 3.21-9.50; 25[OH]D ≤ 16.5 ng/mL, HR 7.46, 95% CI 4.19-13.25). The results were similar when 25[OH]D was examined on a continuous scale (HR per 10-ng/mL decrement in 25[OH]D 2.04, 95% CI 1.65-2.52). The results did not statistically differ by race whether 25[OH]D was examined as a categorical or continuous variable (P interaction > .10)., Conclusions: Lower plasma 25(OH)D concentrations were associated with higher risk of incident CHD. In contrast to prior studies, these associations did not differ by race., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective- Increased Lp(a) [lipoprotein(a)] is associated with coronary heart disease risk, but links with stroke are less consistent. Blacks have higher Lp(a) levels and stroke incidence than whites but have been underrepresented in studies. We hypothesized that Lp(a) is a risk factor for ischemic stroke and that risk differs by race. Approach and Results- REGARDS (Reasons for Geographic and Racial Differences in Stroke) recruited 30 239 black and white US adults aged ≥45 in 2003-2007 to study regional and racial differences in stroke mortality. We measured baseline Lp(a) by immunonephelometric assay in 572 cases of incident ischemic stroke and a 967-person cohort random sample. The hazard ratio of stroke by baseline Lp(a) was calculated using Cox proportional hazards models, stratified by race. Lp(a) was modeled in sex- and race-specific quartiles, given known differences in distributions by race and sex. Interactions were tested by including interaction terms in the proportional hazards models, with P<0.10 considered statistically significant. After adjustment for age, sex, and stroke risk factors, being in the fourth versus the first Lp(a) quartile was weakly associated with ischemic stroke overall, hazard ratio, 1.45 (95% CI, 0.96-2.19). In blacks, the hazard ratio was 1.96 (95% CI, 1.10-3.46), whereas in whites HR was 1.14 (95% CI, 0.64-2.04); P interaction=0.12. Lp(a) was lower in men than women, but associations with stroke in men and women were similar. Conclusions- We confirm that Lp(a) is a risk factor for ischemic stroke. Further research is needed to confirm the role of racial differences of the Lp(a) risk multiplier in ischemic stroke.

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.

Background: Prior studies have consistently demonstrated that blacks have an approximate 2-fold higher incidence of sudden cardiac death (SCD) than whites; however, these analyses have lacked individual-level sociodemographic, medical comorbidity, and behavioral health data., Objectives: The purpose of this study was to evaluate whether racial differences in SCD incidence are attributable to differences in the prevalence of risk factors or rather to underlying susceptibility to fatal arrhythmias., Methods: The Reasons for Geographic and Racial Differences in Stroke study is a prospective, population-based cohort of adults from across the United States. Associations between race and SCD defined per National Heart, Lung, and Blood Institute criteria were assessed., Results: Among 22,507 participants (9,416 blacks and 13,091 whites) without a history of clinical cardiovascular disease, there were 174 SCD events (67 whites and 107 blacks) over a median follow-up of 6.1 years (interquartile range: 4.6 to 7.3 years). The age-adjusted SCD incidence rate (per 1,000 person-years) was higher in blacks (1.8; 95% confidence interval [CI]: 1.4 to 2.2) compared with whites (0.7; 95% CI: 0.6 to 0.9), with an unadjusted hazard ratio of 2.35; 95% CI: 1.74 to 3.20. The association of black race with SCD risk remained significant after adjustment for sociodemographics, comorbidities, behavioral measures of health, intervening cardiovascular events, and competing risks of non-SCD mortality (hazard ratio: 1.97; 95% CI: 1.39 to 2.77)., Conclusions: In a large biracial population of adults without a history of cardiovascular disease, SCD rates were significantly higher in blacks as compared with whites. These racial differences were not fully explained by demographics, adverse socioeconomic measures, cardiovascular risk factors, and behavioral measures of health., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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.

Background and Purpose: Liver disease, particularly non-alcoholic fatty liver disease (NAFLD), is a risk factor for cardiovascular disease, but little is known about its relationship with ischemic stroke., Methods: In the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort of 30,239 American black and white adults, we assessed baseline NAFLD as fatty liver index (FLI) >60, and assessed liver biomarkers aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), and the AST/ALT ratio and risk of incident ischemic stroke over 5.8 years using a case-cohort study design., Results: Considering 572 strokes and a 1,017-person cohort sample, NAFLD was inversely associated with stroke risk in men (HR: 0.50; 95% CI: 0.26, 0.96), as was being in the highest ALT quintile versus the lowest (HR: 0.39; 95% CI: 0.19, 0.78) and the highest versus lowest GGT quintile (HR: 0.45, 95% CI: 0.24, 0.85), but not in women. Conversely, FLI score above the 90th percentile was associated with increased stroke risk among women (HR: 2.26; 95% CI: 1.14-4.47), but not men. AST was not associated with stroke risk in either sex. AST/ALT ratio >2 was strongly associated with increased stroke risk in whites, but not blacks (HRs: 3.64; 95% CI: 1.42-9.35 and 0.97; 95% CI: 0.45-1.99, respectively; p for interaction = 0.03)., Conclusions: The relationships between NAFLD, liver biomarkers, and ischemic stroke are complex, and sex and race differences we observed require further study and confirmation.

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.

Background: PCSK9 loss-of-function (LOF) variants allow for the examination of the effects of lifetime reduced low-density lipoprotein cholesterol (LDL-C) on cardiovascular events. We examined the association of PCSK9 LOF variants with LDL-C and incident coronary heart disease and stroke through a meta-analysis of data from 8 observational cohorts and 1 randomized trial of statin therapy., Methods and Results: These 9 studies together included 17 459 blacks with 403 (2.3%) having at least 1 Y142X or C679X variant and 31 306 whites with 955 (3.1%) having at least 1 R46L variant. Unadjusted odds ratios for associations between PCSK9 LOF variants and incident coronary heart disease (851 events in blacks and 2662 events in whites) and stroke (523 events in blacks and 1660 events in whites) were calculated using pooled Mantel-Haenszel estimates with continuity correction factors. Pooling results across studies using fixed-effects inverse-variance-weighted models, PCSK9 LOF variants were associated with 35 mg/dL (95% confidence interval [CI], 32-39) lower LDL-C in blacks and 13 mg/dL (95% CI, 11-16) lower LDL-C in whites. PCSK9 LOF variants were associated with a pooled odds ratio for coronary heart disease of 0.51 (95% CI, 0.28-0.92) in blacks and 0.82 (95% CI, 0.63-1.06) in whites. PCSK9 LOF variants were not associated with incident stroke (odds ratio, 0.84; 95% CI, 0.48-1.47 in blacks and odds ratio, 1.06; 95% CI, 0.80-1.41 in whites)., Conclusions: PCSK9 LOF variants were associated with lower LDL-C and coronary heart disease incidence. PCSK9 LOF variants were not associated with stroke risk., (© 2017 American Heart Association, Inc.)

Background: Despite a higher prevalence of risk factors, atrial fibrillation (AF) is less prevalent in blacks than whites. To address this paradox, we examined racial differences in the magnitude of AF risk associated with common risk factors., Methods: Participants (13,688; mean age = 63 ± 8.4 years; 56 % female; 37 % black) from the Reasons for Geographic And Racial Differences in Stroke study who were free of baseline AF were included. Incident AF was identified at a follow-up examination by electrocardiogram and self-reported medical history. Poisson regression was used to compute relative risk (RR) and 95 % confidence intervals (CI) for the association between risk factors and incident AF in blacks and whites, separately. Age- and sex-adjusted population attributable fractions (PAFs) of modifiable AF risk factors were computed., Results: After median follow-up of 9.4 years, 997 (7.3 %) incident AF cases were detected. Black race was associated with a lower risk of AF (RR = 0.46, 95 % CI = 0.39, 0.53). Significant risk factors for AF were age, male sex, hypertension, obesity, and cardiovascular disease. A differential association was detected for smoking by race, with the association being stronger in blacks (RR = 1.41, 95 % CI = 1.07, 1.85) compared with whites (RR = 1.01, 95 % CI = 0.88, 1.16; P interaction = 0.030). The PAFs for hypertension (blacks = 27.4 %, whites = 19.4 %), obesity (blacks = 16.9 %, whites = 11.8 %), and smoking (blacks = 17.9 %, whites = 2.5 %) were higher for blacks than whites., Conclusion: Modifiable risk factors are important in AF development among blacks despite a lower risk of the arrhythmia. Racial differences in the magnitude of the association of individual AF risk factors do not explain the AF paradox.

Background: Kidney disease has been associated with venous thromboembolism (VTE) risk, but results conflict and there is little information regarding blacks., Study Design: Prospective cohort study., Setting & Participants: 30,239 black and white adults 45 years or older enrolled in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study 2003 to 2007., Predictors: Estimated glomerular filtration rate (eGFR) using the combined creatinine-cystatin C (eGFR cr-cys ) equation and urinary albumin-creatinine ratio (ACR)., Outcomes: The primary outcome was adjudicated VTE, and secondary outcomes were provoked and unprovoked VTE, separately. Mortality was a competing-risk event., Results: During 4.6 years of follow-up, 239 incident VTE events occurred over 124,624 person-years. Cause-specific HRs of VTE were calculated using proportional hazards regression adjusted for age, sex, race, region of residence, and body mass index. Adjusted VTE HRs for eGFR cr-cys of 60 to <90, 45 to <60, and <45 versus ≥90mL/min/1.73m 2 were 1.28 (95% CI, 0.94-1.76), 1.30 (95% CI, 0.77-2.18), and 2.13 (95% CI, 1.21-3.76). Adjusted VTE HRs for ACR of 10 to <30, 30 to <300, and ≥300 versus <10mg/g were 1.14 (95% CI, 0.84-1.56), 1.15 (95% CI, 0.79-1.69), and 0.64 (95% CI, 0.25-1.62). Associations were similar for provoked and unprovoked VTE., Limitations: Single measurement of eGFR and ACR may have led to misclassification. Smaller numbers of events may have limited power., Conclusions: There was an independent association of low eGFR (<45 vs ≥90mL/min/1.73m 2 ) with VTE risk, but no association of ACR and VTE., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

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 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 =0.7075; 95% confidence interval, 0.6877-0.7273; 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.)

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.

Marked racial differences exist in dietary patterns and obesity, as well as cancer mortality. This study aims to assess whether dietary patterns are associated with cancer mortality overall and by race. We identified 22,041 participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Dietary patterns were categorized into: Convenience (Chinese and Mexican foods, pasta, pizza), Plant-based (fruits, vegetables), Southern (added fats, fried foods, sugar-sweetened beverages), Sweets/Fats (sugary foods) and Alcohol/Salads (alcohol, green-leafy vegetables, salad dressing). Using Cox regression, we examined the association between quartiles of dietary patterns and cancer mortality, adjusted for potential confounders, overall among all participants and stratified by race. A total of 873 cancer deaths were observed over the 10-year observation period: 582 (66.7%) in Whites and 291 (33.3%) in Blacks. Greater adherence to the Southern dietary pattern was associated with an increased risk of cancer mortality (4th vs. 1st quartile HR: 1.67; 95% CI: 1.32-2.10) overall, especially among Whites (4th vs. 1st quartile HR: 1.59; 95% CI: 1.22-2.08). The convenience (HR: 0.73; 95% CI: 0.56-0.94) and Plant-based (HR: 0.72; 95% CI: 0.55-0.93) dietary patterns were associated with up to a 28% reduced risk of cancer mortality, but only among Whites. Greater adherence to the Southern dietary pattern increased the risk of cancer mortality, while greater adherence to the convenience and Plant-based diets reduced the risk of cancer mortality among Whites. Racial differences were observed in the association between dietary patterns and cancer mortality, but warrant further study., (© 2016 UICC.)

Background and Purpose: At age 45 years, blacks have a stroke mortality ≈3× greater than their white counterparts, with a declining disparity at older ages. We assess whether this black-white disparity in stroke mortality is attributable to a black-white disparity in stroke incidence versus a disparity in case fatality., Methods: We first assess if black-white differences in stroke mortality within 29 681 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort reflect national black-white differences in stroke mortality and then assess the degree to which black-white differences in stroke incidence or 30-day case fatality after stroke contribute to the disparities in stroke mortality., Results: The pattern of stroke mortality within the study mirrors the national pattern, with the black-to-white hazard ratio of ≈4.0 at age 45 years decreasing to ≈1.0 at age 85 years. The pattern of black-to-white disparities in stroke incidence shows a similar pattern but no evidence of a corresponding disparity in stroke case fatality., Conclusions: These findings show that the black-white differences in stroke mortality are largely driven by differences in stroke incidence, with case fatality playing at most a minor role. Therefore, to reduce the black-white disparity in stroke mortality, interventions need to focus on prevention of stroke in blacks., (© 2016 American Heart Association, Inc.)

Objectives: To assess whether black race and other cerebrovascular risk factors have a differential effect on first vs. recurrent stroke events., Methods: Estimate the differences in the magnitude of the association of demographic (age, back race, sex) or stroke risk factors (hypertension, diabetes, cigarette smoking, atrial fibrillation, left ventricular hypertrophy, or heart disease) for first vs. recurrent stroke from a longitudinal cohort study of 29,682 black or white participants aged 45 years and older., Results: Over an average 6.8 years follow-up, 301 of 2,993 participants with a previous stroke at baseline had a recurrent stroke, while 818 of 26,689 participants who were stroke-free at baseline had a first stroke. Among those stroke-free at baseline, there was an age-by-race interaction (p = 0.0002), with a first stroke risk 2.70 (95% confidence interval: 1.86-3.91) times greater for black than white participants at age 45, but no racial disparity at age 85 (hazard ratio = 0.91; 95% confidence interval: 0.70-1.18). In contrast, there was no evidence of a higher risk of recurrent stroke at any age for black participants (p > 0.05). The association of traditional stroke risk factors was generally similar for first and recurrent stroke., Conclusion: The association of age and black race differs substantially on first vs. recurrent stroke risk, with risk factors playing a similar role., (© 2016 American Academy of Neurology.)

It is unclear if patients who have atrial fibrillation (AF) have a greater fall risk compared with those in the general population and if falls increase mortality beyond that observed in AF. A total of 24,117 (mean age 65 ± 9.3 years; 55% women; 38% black) participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were included. AF was identified from baseline electrocardiogram data and by self-reported history. Falls were considered present if participants reported ≥2 falls within the year before the baseline examination. Logistic regression was used to examine the relationship between prevalent AF and falls. Cox regression was used to examine the risk of death in those with AF and falls, separately and in combination, compared with those without either condition. A total of 2,007 participants (8.3%) had baseline AF and 1,655 (6.7%) reported falls. A higher prevalence of falls was reported in those with AF (n = 209; 10%) than those without AF (n = 1,446; 6.5%; p <0.0001). After adjustment for fall risk factors, AF was significantly associated with falls (odds ratio 1.22, 95% confidence interval [CI] 1.04 to 1.44). Compared with no history of AF or falls, the concomitant presence of AF and falls (hazard ratio [HR] 2.12, 95% CI 1.64 to 2.74) was associated with a greater risk of death than AF (HR 1.44, 95% CI 1.28 to 1.62) or falls (HR 1.61, 95% CI 1.42 to 1.82). In conclusion, patients with AF are more likely to report a history of falls in REGARDS. Additionally, participants with AF who report falls have an increased risk of death than those with either condition in isolation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The association of overall diet, as characterized by dietary patterns, with risk of incident acute coronary heart disease (CHD) has not been studied extensively in samples including sociodemographic and regional diversity., Methods and Results: We used data from 17 418 participants in Reasons for Geographic and Racial Differences in Stroke (REGARDS), a national, population-based, longitudinal study of white and black adults aged ≥45 years, enrolled from 2003 to 2007. We derived dietary patterns with factor analysis and used Cox proportional hazards regression to examine hazard of incident acute CHD events - nonfatal myocardial infarction and acute CHD death - associated with quartiles of consumption of each pattern, adjusted for various levels of covariates. Five primary dietary patterns emerged: Convenience, Plant-based, Sweets, Southern, and Alcohol and Salad. A total of 536 acute CHD events occurred over a median (interquartile range) 5.8 (2.1) years of follow-up. After adjustment for sociodemographics, lifestyle factors, and energy intake, highest consumers of the Southern pattern (characterized by added fats, fried food, eggs, organ and processed meats, and sugar-sweetened beverages) experienced a 56% higher hazard of acute CHD (comparing quartile 4 with quartile 1: hazard ratio, 1.56; 95% confidence interval, 1.17-2.08; P for trend across quartiles=0.003). Adding anthropometric and medical history variables to the model attenuated the association somewhat (hazard ratio, 1.37; 95% confidence interval, 1.01-1.85; P=0.036)., Conclusions: A dietary pattern characteristic of the southern United States was associated with greater hazard of CHD in this sample of white and black adults in diverse regions of the United States., (© 2015 American Heart Association, Inc.)

Background: Blacks are thought to have a higher risk of venous thromboembolism (VTE) than whites. However, prior studies are limited to administrative databases that lack specific information on VTE risk factors or have limited geographic scope., Methods and Results: We ascertained VTE from 3 prospective studies: the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Health Study (CHS), and the Reasons for Geographic and Racial Differences in Stroke study (REGARDS). We tested the association of race with VTE using Cox proportional hazard models adjusted for VTE risk factors. Over 438 090 person-years, 916 incident VTE events (302 in blacks) occurred in 51 149 individuals (17 318 blacks) who were followed up. In risk factor-adjusted models, blacks had a higher rate of VTE than whites in the CHS (hazard ratio, 1.81; 95% confidence interval, 1.20-2.73) but not ARIC (hazard ratio, 1.21; 95% confidence interval, 0.96-1.54). In REGARDS, there was a significant region-by-race interaction (P=0.01): Blacks in the Southeast had a significantly higher rate of VTE than blacks in the rest of the United States (hazard ratio, 1.63; 95% confidence interval, 1.08-2.48) that was not seen in whites (hazard ratio, 0.83; 95% confidence interval, 0.61-1.14)., Conclusions: The association of race with VTE differed in each cohort, which may reflect the different time periods of the studies or different regional rates of VTE. Further studies of environmental and genetic risk factors for VTE are needed to determine which underlie racial and perhaps regional differences in VTE.

Sunlight may be related to cognitive function through vitamin D metabolism or circadian rhythm regulation. The analysis presented here sought to test whether ground and satellite measures of solar radiation are associated with cognitive decline. The study used a 15-year residential history merged with satellite and ground monitor data to determine sunlight (solar radiation) and air temperature exposure for a cohort of 19,896 cognitively intact black and white participants aged 45+ from the 48 contiguous United States. Exposures of 15, 10, 5, 2, and 1-year were used to predict cognitive status at the most recent assessment in logistic regression models; 1-year insolation and maximum temperatures were chosen as exposure measures. Solar radiation interacted with temperature, age, and gender in its relationships with incident cognitive impairment. After adjustment for covariates, the odds ratio (OR) of cognitive decline for solar radiation exposure below the median vs above the median in the 3rd tertile of maximum temperatures was 1.88 (95 % CI: 1.24, 2.85), that in the 2nd tertile was 1.33 (95 % CI: 1.09, 1.62), and that in the 1st tertile was 1.22 (95 % CI: 0.92, 1.60). We also found that participants under 60 years old had an OR = 1.63 (95 % CI: 1.20, 2.22), those 60-80 years old had an OR = 1.18 (95 % CI: 1.02, 1.36), and those over 80 years old had an OR = 1.05 (0.80, 1.37). Lastly, we found that males had an OR = 1.43 (95 % CI: 1.22, 1.69), and females had an OR = 1.02 (0.87, 1.20). We found that lower levels of solar radiation were associated with increased odds of incident cognitive impairment.

Background: Between the ages 45 and 65 years, incident stroke is 2 to 3 times more common in blacks than in whites, a difference not explained by traditional stroke risk factors., Methods: Stroke risk was assessed in 27 748 black and white participants recruited between 2003 and 2007, who were followed up through 2011, in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Racial differences in the impact of systolic blood pressure (SBP) was assessed using proportional hazards models. Racial differences in stroke risk were assessed in strata defined by age (<65 years, 65-74 years, and ≥75 years) and SBP (<120 mm Hg, 120-139 mm Hg, and 140-159 mm Hg)., Results: Over 4.5 years of follow-up, 715 incident strokes occurred. A 10-mm Hg difference in SBP was associated with an 8% (95% CI, 0%-16%) increase in stroke risk for whites, but a 24% (95% CI, 14%-35%) increase for blacks (P value for interaction, .02). For participants aged 45 to 64 years (where disparities are greatest), the black to white hazard ratio was 0.87 (95% CI, 0.48-1.57) for normotensive participants, 1.38 (95% CI, 0.94-2.02) for those with prehypertension, and 2.38 (95% CI, 1.19-4.72) for those with stage 1 hypertension., Conclusions: These findings suggest racial differences in the impact of elevated blood pressure on stroke risk. When these racial differences are coupled with the previously documented higher prevalence of hypertension and poorer control of hypertension in blacks, they may account for much of the racial disparity in stroke risk.

Objective: Examine whether long- and short-term sunlight radiation is related to stroke incidence., Methods: Fifteen-year residential histories merged with satellite, ground monitor, and model reanalysis data were used to determine sunlight radiation (insolation) and temperature exposure for a cohort of 16,606 stroke and coronary artery disease-free black and white participants aged ≥45 years from the 48 contiguous United States. Fifteen-, 10-, 5-, 2-, and 1-year exposures were used to predict stroke incidence during follow-up in Cox proportional hazard models. Potential confounders and mediators were included during model building., Results: Shorter exposure periods exhibited similar, but slightly stronger relationships than longer exposure periods. After adjustment for other covariates, the previous year's monthly average insolation exposure below the median gave a hazard ratio (HR) of 1.61 (95% confidence interval [CI], 1.15-2.26), and the previous year's highest compared to the second highest quartile of monthly average maximum temperature exposure gave an HR of 1.92 (95%, 1.27-2.92)., Interpretation: These results indicate a relationship between lower levels of sunlight radiation and higher stroke incidence. The biological pathway of this relationship is not clear. Future research will show whether this finding stands, the pathway for this relationship, and whether it is due to short- or long-term exposures., (Copyright © 2012 American Neurological Association.)

Background and Purpose: History of stroke and transient ischemic attack (TIA) are documented risk factors for subsequent stroke and all-cause mortality. Recent reports suggest increased risk among those reporting stroke symptoms absent stroke or TIA. However, the relative magnitude of increased stroke risk has not been described across the symptomatic spectrum: (1) asymptomatic, (2) stroke symptoms (SS) only, (3) TIA, (4) distant stroke (DS), and (5) recent stroke (RS)., Methods: Between 2003 and 2007, the REasons for Geographic And Racial Differences in Stroke (REGARDS) study enrolled 30 239 black and white Americans ≥45 years of age. DS and RS were defined as self-report of physician diagnosis of stroke >5 or <5 years before baseline, respectively. SS was defined as a history of any of 6 sudden onset stroke symptoms absent TIA/stroke diagnosis. Kaplan-Meier and proportional hazards analysis were used to contrast stroke risk differences., Results: Over 5.0±1.72 years of follow-up, 737 strokes were validated. Compared with asymptomatic persons, those with SS, TIA, DS, and RS all had increased risk of future stroke. After adjustment for age, race, sex, income, education, alcohol intake, current smoking, and a history of diabetes mellitus, hypertension, myocardial infarction, atrial fibrillation, and dyslipidemia, there was 1.20-fold (not statistically significant) increased stroke risk for SS (95% CI, 0.96-1.51), 1.73-fold for TIA (95% CI, 1.27-2.36), 2.23-fold for DS (95% CI, 1.61- 3.09), and 2.85-fold for RS (95% CI, 2.16-3.76)., Conclusions: Results suggest a spectrum of risk from stroke symptoms to TIA, DS, and RS, and imply a need for establishing these categories in health screenings to manage risk for future stroke, reinforcing the clinical importance of stroke history including the presence of stroke symptoms.

Background: The objective of this study was to examine the joint associations of estimated glomerular filtration rate (eGFR) and urinary albumin excretion with incident stroke in a large national cohort study., Methods: Associations of urinary albumin to creatinine ratio (ACR) and eGFR with incident stroke were examined in 25,310 participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a prospective study of black and white US adults ≥45 years of age., Results: A total of 548 incident strokes were observed over a median of 4.7 years of follow-up. Higher ACR values were associated with lower stroke-free survival in both black and white participants. Among black participants, as compared to an ACR <10 mg/g, the hazard ratios of stroke associated with an ACR of 10-29.99, 30-300, and >300 mg/g were 1.41 (95% confidence interval [CI] 1.01-1.98), 2.10 (95% CI 1.48-2.99), and 2.70 (95% CI 1.58-4.61), respectively, in analyses adjusted for traditional stroke risk factors and eGFR. In contrast, the hazard ratios among white subjects were only modestly elevated and not statistically significant after adjustment for established stroke risk factors. eGFR <60 mL/min/1.73 m(2) was not associated with incident stroke in black or white participants after adjustment for established stroke risk factors., Conclusions: Higher ACR was independently associated with higher risk of stroke in black but not white participants from a national cohort. Elucidating the reasons for these findings may uncover novel mechanisms for persistent racial disparities in stroke.

Objective: While black-white and regional disparities in U.S. stroke mortality rates are well documented, the contribution of disparities in stroke incidence is unknown. We provide national estimates of stroke incidence by race and region, contrasting these to publicly available stroke mortality data., Methods: This analysis included 27,744 men and women without prevalent stroke (40.4% black), aged ≥45 years from the REasons for Geographic And Racial Differences in Stroke (REGARDS) national cohort study, enrolled 2003-2007. Incident stroke was defined as first occurrence of stroke over 4.4 years of follow-up. Age-sex-adjusted stroke mortality rates were calculated using data from the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiological Research (WONDER) System., Results: There were 460 incident strokes over 113,469 person-years of follow-up. Relative to the rest of the United States, incidence rate ratios (IRRs) of stroke in the southeastern stroke belt and stroke buckle were 1.06 (95% confidence interval [CI], 0.87-1.29) and 1.19 (95% CI, 0.96-1.47), respectively. The age-sex-adjusted black/white IRR(black) was 1.51 (95% CI, 1.26-1.81), but for ages 45-54 years the IRR(black) was 4.02 (95% CI, 1.23-13.11) while for ages 85+ it was 0.86 (95% CI, 0.33-2.20). Generally, the IRRs(black) were less than the mortality rate ratios (MRRs) across age groups; however, only in ages 55-64 years and 65-74 years did the 95% CIs of IRRs(black) not include the MRR(black) . The MRRs for regions were within 95% CIs for IRRs., Interpretation: National patterns of black-white and regional differences in stroke incidence are similar to those for stroke mortality; however, the magnitude of differences in incidence appear smaller., (Copyright © 2011 American Neurological Association.)

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

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. [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]

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 socioeco- nomic 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. [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 association between perceived stress and atrial fibrillation (AF) remains unclear.Purpose: The aim of this study was to examine the association between perceived stress and AF.Methods: A total of 25,530 participants (mean age 65 ± 9.4 years; 54 % women; 41 % blacks) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were included in this analysis. Logistic regression was used to compute odds ratios (OR) and 95 % confidence intervals (CI) for the association between the short version of the Cohen Perceived Stress Scale and AF.Results: In a multivariable analysis adjusted for demographics, cardiovascular risk factors, and potential confounders, the prevalence of AF was found to increase with higher levels of stress (none: OR = 1.0, referent; low stress: OR = 1.12, 95 % CI = 0.98, 1.27; moderate stress OR = 1.27, 95 % CI = 1.11, 1.47; high stress: OR = 1.60, 95 % CI = 1.39, 1.84).Conclusion: Increasing levels of perceived stress are associated with prevalent AF in REGARDS. [ABSTRACT FROM AUTHOR]

Background: Healthy obese individuals may be protected against adverse health outcomes. Diet and race might influence healthy obesity, but data on their roles and interactions on the phenotype are limited.Objective: We compared the food intake of metabolically healthy obese men to those of other weight status-metabolic health phenotypes.Methods: Men (n = 4855) aged ≥ 45 y with BMI ≥ 18.5 kg/m(2) and free of cardiovascular diseases, diabetes, and cancer were evaluated in a cross-sectional study of the REGARDS (REasons for Geographic And Racial Differences in Stroke) study cohort. Food intake was assessed with the use of a food frequency questionnaire. Weight status-metabolic health phenotypes were defined by using metabolic syndrome (MetS) and homeostasis model assessment of insulin resistance (HOMA-IR) criteria. Mean differences in food intake among weight status-metabolic health phenotypes were compared with the use of linear regression.Results: MetS-defined healthy obesity was present in 44% of white obese men and 58% of black obese men; the healthy obese phenotype, based on HOMA-IR, was equally prevalent in both white (20%) and black (21%) obese men. Among white men, MetS-defined healthy and unhealthy obesity were associated with lower wholegrain bread intake and higher consumption of red meat (P < 0.001), whereas HOMA-IR-defined healthy and unhealthy obesity were associated with lower red meat intake (P < 0.0001) compared with healthy normal weight in multivariable-adjusted analyses that adjusted for sociodemographic, lifestyle, and clinical confounders. However, results were attenuated and became nonsignificant after further adjustment for BMI. Healthy and unhealthy overweight, defined by both criteria, were associated with lower whole grain bread intake (P < 0.001) in all models. Among black men, weight status-metabolic health phenotypes were not associated with food intake in all models.Conclusion: Healthy obesity in men is not associated with a healthier diet. Future studies need to consider dietary patterns, which may better inform the holistic effect of diet on healthy obesity, in prospective analyses. [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]