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Background: Few national studies across the United States' rural-urban continuum examine neighborhood effects on snacks and sweets intake among adults., Objectives: This study examines associations of urbanicity/rurality-tailored measures of food store availability and neighborhood socioeconomic status (NSES) with the intake of snacks and sweets in a national sample of middle and older age adults., Methods: This cross-sectional study used food frequency questionnaire data collected in the REasons for Geographic And Racial Differences in Stroke study (N = 21,204). What We Eat in America food group categorizations guided outcome classification into 1 main category (total snacks and sweets) and 4 subcategories (savory snacks and crackers; sweet bakery products; candy and desserts; nutrition bars and low-fat snacks and sweets). NSES and food store availability were determined using geographic information systems. Food store availability was characterized as geographic access to primary food stores (e.g., supermarkets, supercenters, and select food retailers) in urbanicity/rurality-tailored neighborhood-based buffers. Multiple linear regression was used to predict each outcome., Results: Living in neighborhoods with a high density of primary food stores was associated with 8.6%, 9.5%, and 5.8% lower intake of total snacks and sweets, sweet bakery products, and candy and desserts, respectively. Living in the highest NSES quartile was associated with 11.3%, 5.8%, and 18.9% lower intake of total snacks and sweets, savory snacks and crackers, and sweet bakery products, respectively. Depending on primary food store availability, higher household income was associated with significantly greater intake of nutrition bars and low-fat snacks and sweets. Living in a United States Department of Agriculture-defined food desert was not associated with intake., Conclusions: In a geographically diverse sample of middle and older age United States adults, living in neighborhoods with no primary food stores or neighborhoods of low-SES was associated with higher intake of total snacks and sweets and subgroups of snacks and sweets., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Hepatocyte growth factor (HGF) is a cytokine produced in response to endothelial damage. Higher levels correlate with cardiovascular risk factors, including hypertension and diabetes., Objectives: We hypothesized that HGF is associated with stroke., Methods: The Reasons for Geographic And Racial Differences in Stroke (REGARDS) study enrolled 30,239 Black and White Americans aged ≥45 years from 2003 to 2007. In this case-cohort study, after 5.5 years of follow-up, circulating baseline HGF was measured in 557 participants with incident ischemic stroke and in a cohort random sample of 964 participants. Hazard ratios (HRs) per SD log-transformed HGF and by HGF quintile were calculated using Cox proportional hazards models adjusting for stroke risk factors and other correlates of HGF. Differences by race and sex were tested using interaction terms., Results: Median HGF was 295 (IQR, 209-402) pg/mL. HGF was higher with older age, male sex, prevalent cardiovascular disease, smoking, and warfarin use, but did not differ by race. The adjusted HR of incident ischemic stroke per SD higher baseline HGF (145 pg/mL) was 1.30 (CI, 1.00-1.70), with no difference by sex or race. HGF in the highest (>434 pg/mL) vs lowest quintile (<135 pg/mL) was associated with an adjusted HR of incident stroke of 2.12 (CI, 1.31-3.41)., Conclusion: In the REGARDS study, higher HGF was associated with increased risk of incident ischemic stroke in Black and White adults, with a doubling in risk of HGF in the top quintile compared with the lowest quintile after adjusting for other stroke risk factors., (© 2024 Published by Elsevier Inc. on behalf of International Society on Thrombosis and Haemostasis.)

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

Background: Reasons for increased risk of hypertension in Black compared with White people are only partly understood. D-dimer, a thrombo-inflammatory marker higher in Black individuals, is also higher in people with hypertension. However, the impact of D-dimer on racial disparities in risk of incident hypertension has not been studied., Objectives: To assess whether D-dimer is associated with the risk of incident hypertension, whether the association between D-dimer and the risk of incident hypertension differs by race, and whether the biology reflected by D-dimer explains racial disparities in the risk of incident hypertension., Methods: This study included 1867 participants in the REasons for Geographic And Racial Differences in Stroke cohort study without baseline hypertension and with a second visit 9.4 years after baseline. Risk ratios of incident hypertension by baseline D-dimer level were estimated, a D-dimer-by-race interaction was tested, and the mediating effect of D-dimer (which represents underlying biological processes) on the association of race and hypertension risk was assessed., Results: The risk of incident hypertension was 47% higher in persons in the top quartile than in those in the bottom quartile of D-dimer (risk ratio [RR]: 1.47; 95% CI: 1.23-1.76). The association was partly attenuated after adjusting for sociodemographic and adiposity-related risk factors (RR: 1.22; 95% CI: 1.02-1.47). The association of D-dimer and hypertension did not differ by race, and D-dimer did not attenuate the racial difference in the risk of incident hypertension., Conclusion: D-dimer concentration reflects pathophysiology related to the development of hypertension. Specific mechanisms require further study and may involve adiposity., (© 2022 The Authors.)

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

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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: Higher D-dimer is a risk factor for cardiovascular diseases and venous thromboembolism. In the general population, D-dimer and other thrombo-inflammatory biomarkers are higher among Black individuals, who also have higher risk of these conditions compared to White people., Objective: To assess whether Black individuals have an exaggerated correlation between D-dimer and thrombo-inflammatory biomarkers characteristic of cardiovascular diseases., Methods: Linear regression was used to assess correlations of 11 thrombo-inflammatory biomarkers with D-dimer in a cross-sectional study of 1068 participants of the biracial Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort., Results: Adverse levels of most biomarkers, especially fibrinogen, factor VIII, C-reactive protein, N-terminal pro-B-type natriuretic peptide, and interleukin (IL)-6, were associated with higher D-dimer. Several associations with D-dimer differed significantly by race. For example, the association of factor VIII with D-dimer was more than twice as large in Black compared to White participants. Specifically, D-dimer was 26% higher per standard deviation (SD) higher factor VIII in Black adults and was only 11% higher per SD higher factor VIII in White adults. In Black but not White adults, higher IL-10 and soluble CD14 were associated with higher D-dimer., Conclusions: Findings suggest that D-dimer might relate to Black/White differences in cardiovascular diseases and venous thromboembolism because it is a marker of amplified thrombo-inflammatory response in Black people. Better understanding of contributors to higher D-dimer in the general population is needed., (© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Purpose: To examine how the choice of neighborhood food environment definition impacts the association with diet., Methods: Using food frequency questionnaire data from the Reasons for Geographic and Racial Differences in Stroke study at baseline (2003-2007), we calculated participants' dietary inflammation score (DIS) (n = 20,331); higher scores indicate greater pro-inflammatory exposure. We characterized availability of supermarkets and fast food restaurants using several geospatial measures, including density (i.e., counts/km 2 ) and relative measures (i.e., percentage of all food stores or restaurants); and various buffer distances, including administrative units (census tract) and empirically derived buffers ("classic" network, "sausage" network) tailored to community type (higher density urban, lower density urban, suburban/small town, rural). Using generalized estimating equations, we estimated the association between each geospatial measure and DIS, controlling for individual- and neighborhood-level sociodemographics., Results: The choice of buffer-based measure did not change the direction or magnitude of associations with DIS. Effect estimates derived from administrative units were smaller than those derived from tailored empirically derived buffer measures. Substantively, a 10% increase in the percentage of fast food restaurants using a "classic" network buffer was associated with a 6.3 (SE = 1.17) point higher DIS (P< .001). The relationship between the percentage of supermarkets and DIS, however, was null. We observed high correlation coefficients between buffer-based density measures of supermarkets and fast food restaurants (r = 0.73-0.83), which made it difficult to estimate independent associations by food outlet type., Conclusions: Researchers should tailor buffer-based measures to community type in future studies, and carefully consider the theoretical and statistical implications for choosing relative (vs. absolute) measures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Aims: Data on the relation of egg consumption with risk of type 2 diabetes (T2D) and coronary heart disease (CHD) are limited and inconsistent. Few studies have controlled for overall dietary patterns in egg-T2D or egg-CHD analyses, and it is unclear whether any observed elevated risks of T2D and CHD with frequent egg consumption is real or due to confounding by dietary habits. We tested the hypothesis that frequent egg consumption is associated with a higher risk of T2D and CHD risk after adjustment for overall dietary patterns among adults., Design: We used prospective cohort design to complete time-to-event analyses., Methods: We pooled de novo, harmonized, individual-level analyses from nine US cohorts (n = 103,811). Cox regression was used to estimate hazard ratios separately in each cohort adjusting for age, ethnicity, body mass index (BMI), exercise, smoking, alcohol intake, and dietary patterns. We pooled cohort-specific results using an inverse-variance weighted method to estimate summary relative risks., Results: Median age ranged from 25 to 72 years. Median egg consumption was 1 egg per week in most of the cohorts. While egg consumption up to one per week was not associated with T2D risk, consumption of ≥2 eggs per week was associated with elevated risk [27% elevated risk of T2D comparing 7+ eggs/week with none (95% CI: 16%-37%)]. There was little evidence for heterogeneity across cohorts and we observed similar conclusions when stratified by BMI. Overall, egg consumption was not associated with the risk of CHD. However, in a sensitivity analysis, there was a 30% higher risk of CHD (95% CI: 3%-56%) restricted to older adults consuming 5-6 eggs/week., Conclusions: Our data showed an elevated risk of T2D with egg consumption of ≥2 eggs per week but not with <2 eggs/week. While there was no overall association of egg consumption with CHD risk, the elevated CHD observed with consumption of 5-6 eggs/week in older cohorts merits further investigation., Competing Interests: Disclosures Dr. Djousse received investigator-initiated grant from American Egg Board for current analyses; sponsor had no influence on design, conduct, and interpretation of the results. Other co-authors have no disclosures., (Published by Elsevier Ltd.)

Objective: To investigate the longitudinal association between magnesium (Mg) intake and the risk of metabolic syndrome (MetS)., Methods: Poisson regression models with robust standard error estimation were used to examine the association between total Mg intake and the risk of MetS in 6802 participants aged ≥45 years at baseline in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Dietary data were collected using the modified Block 98 food frequency questionnaire (FFQ) at baseline and incident MetS was diagnosed during follow-up if a participant had three or more of the five components of MetS based on the harmonized definition., Results: A total of 1470 participants developed MetS during an average follow-up of 10 years. Comparing the highest quintile of total Mg intake (>437.9 mg/day) to the lowest group (<223.5 mg/day), total Mg intake had a significant inverse association with the risk of MetS [relative risk (RR) = 0.79 (0.63, 0.98), P trend  = 0.043]. Dietary Mg intake was inversely associated with MetS [RR = 0.72 (0.56, 0.91), P trend  = 0.006]. Adjusting for baseline components of MetS attenuated the associations, but the linear trends remained., Conclusion: The findings from this study indicate that dietary Mg intake was inversely associated with the risk of MetS. We recommend further studies to explain the underlying mechanisms of action., Competing Interests: Conflict of interest None of the authors declared any conflict of interest., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP), a commonly used clinical marker of cardiac function, is associated with the presence of stroke symptoms and is a strong risk factor for future atrial fibrillation, stroke, and all-cause mortality. Few data are available on the association between NT-proBNP levels and stroke recurrence., Objective: We studied the relationship between NT-proBNP and risk of future ischemic stroke across the continuum of preexisting cerebrovascular conditions: asymptomatic, prior stroke symptoms, prior transient ischemic attack (TIA), and prior stroke., Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort enrolled 30,239 black and white Americans aged 45 years and older from 2003 to 2007. With 5.4 years follow-up, baseline NT-proBNP was measured in 892 participants who developed ischemic stroke and a 4328-person cohort random sample. Hazard ratios of stroke by baseline NT-proBNP were calculated in groups based on the presence of prebaseline cerebrovascular conditions., Results: In the fully adjusted model, elevated NT-proBNP was associated with stroke risk in participants without a preexisting cerebrovascular condition (hazard ratio [HR], 2.32; 95% confidence interval [CI], 1.84-2.94) and in participants with a history of stroke symptoms (HR, 1.67; 95% CI, 1.01-2.78) or transient ischemic attack (HR, 2.66; 95% CI, 1.00-7.04) but not among those with prior stroke (HR, 1.26; 95% CI, 0.71-2.21)., Conclusions: These findings support the potential for NT-proBNP testing to identify people who are at highest risk for future stroke., (© 2020 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Background: Chronically higher inflammation, which may partly result from diet and lifestyle, is implicated in risk for multiple chronic diseases. The dietary inflammatory index (DII) and empirical dietary inflammatory pattern (EDIP), developed to characterize dietary contributions to systemic inflammation, have several limitations. There are no scores to characterize contributions of lifestyle to inflammation., Objectives: To reflect dietary/lifestyle contributions to inflammation, we developed novel, inflammation biomarker panel-weighted, dietary (DIS) and lifestyle (LIS) inflammation scores in a subset (n = 639) of the Reasons for Geographic and Racial Differences in Stroke Study (REGARDS) cohort., Methods: We selected a priori 19 food groups and 4 lifestyle characteristics to comprise the DIS and LIS, respectively. We calculated the components' weights based on their strengths of association with an inflammation biomarker score [comprising high-sensitivity C-reactive protein (hsCRP), IL-6, IL-8, and IL-10] using multivariable linear regression. The sums of the weighted components constitute the scores, such that higher scores reflect, on balance, more proinflammatory exposures. We calculated the DIS, LIS, DII, and EDIP with cross-sectional data from the remaining REGARDS cohort (  n = 14,210 with hsCRP measurements) and 2 other study populations with hsCRP and/or an 8-component inflammation biomarker panel, and investigated their associations with circulating inflammation biomarker concentrations using multivariable logistic regression., Results: In REGARDS, those in the highest relative to the lowest DIS, LIS, DII, and EDIP quintiles had statistically significant 1.66-, 4.29-, 1.56-, and 1.32-fold higher odds of a high hsCRP concentration (>3 mg/dL), respectively (all P-trend < 0.001). Those in the highest relative to the lowest joint DIS/LIS quintile had a statistically significant 7.26-fold higher odds of a high hsCRP concentration. Similar findings were noted in the other 2 validation populations., Conclusion: Our results support that dietary and lifestyle exposures collectively contribute substantially to systemic inflammation, and support the use of our novel DIS and LIS., (Copyright © American Society for Nutrition 2019.)

Background: Population studies have shown that black race is a natriuretic peptide (NP) deficiency state. We sought to assess whether the effects of age, sex, body mass index (BMI) and estimated glomerular filtration rate (eGFR) on N-terminal-pro-B-type NP (NT-proBNP) levels differ in white and black individuals., Methods: The study population consisted of a stratified random cohort from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. The study outcomes were the effects of age, sex, BMI and eGFR on NT-proBNP levels independent of socioeconomic and cardiovascular disease factors. Multivariable regression analyses were used to assess the effects of age, sex, BMI and eGFR on NT-proBNP levels in blacks and whites., Results: Of the 27,679 participants in the weighted sample, 54.7% were females, 40.6% were black, and the median age was 64 years. Every 10-year higher age was associated with 38% [95% confidence interval (CI): 30%-45%] and 34% (95% CI: 22%-43%) higher NT-proBNP levels in whites and blacks, respectively. Female sex was associated with 31% (95% CI: 20%-43%) higher NT-proBNP levels in whites and 28% (95% CI: 15%-45%) higher in blacks. There was a significant linear inverse relationship between BMI and NT-proBNP in whites and a non-linear inverse relationship in blacks. Whites and blacks had a non-linear inverse relationship between eGFR and NT-proBNP. However, the non-linear relationship between NT-proBNP and eGFR differed by race (p = 0.01 for interaction)., Conclusions: The association of age and sex with NT-proBNP levels was similar in blacks and whites but the form of the BMI and eGFR relationship differed by race., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Retrospective studies have reported an association between cancer and arterial thromboembolic event (ATE) risk., Objectives: We sought to confirm this in a prospective cohort with adjudicated outcomes., Methods: We evaluated participants enrolled in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study with Medicare coverage for 365 days before their baseline visit (2003-2007). Medicare claims were used to identify new cancer diagnoses during follow-up. Using incidence-density sampling, participants who developed cancer were matched by age, sex, race, and education 1:4 to control participants who had not developed cancer. Participants were prospectively followed through 2015 for an expert-adjudicated ATE, defined as acute myocardial infarction or ischemic stroke. Cox regression was performed to evaluate the association between incident cancer and subsequent ATE., Results: In this analysis, 836 REGARDS participants with incident cancer were matched to 3339 control participants without cancer. In the 30 days after cancer diagnosis, 0.60% (n = 5) of the participants had an ATE; most of these events occurred near the time of cancer diagnosis. After adjustment for demographics, geographic region, and cardiovascular risk factors, compared to the noncancer controls, participants with incident cancer had an increased risk of ATE in the first 30 days after diagnosis (hazard ratio, 5.8; 95% confidence interval, 2.1-15.9). There was no association between cancer diagnosis and ATE beyond 30 days. Cancers with known metastases and types considered high risk for venous thromboembolism had the strongest associations with ATE., Conclusions: Incident cancer is associated with an increased short-term risk of ATE independent of vascular risk factors., Competing Interests: GH serves on an executive committee for Bayer HealthCare and previously served as a member of a data and safety monitoring board for a randomized trial sponsored by Alexion. MSVE received compensation for providing consultative services for Abbott, Biotelemetry/Cardionet, BMS‐Pfizer Alliance for Eliquis, Boehringer‐Ingelheim, Sanofi‐Regeneron Partnership, and Vascular Dynamics; received compensation for serving as an expert witness in litigation for BMS‐Sanofi, Merck/Organon, Hi‐Tech Pharmaceuticals, Auxilium, and Sorin; received research support from the BMS‐Pfizer Alliance for Eliquis and Roche; received royalties from UpToDate for chapters related to stroke; and serves on the National, Founders Affiliate, and New York City chapter boards of the American Heart Association/American Stroke Association. CI served on the scientific advisory board for Broadview Ventures. LMD served on scientific advisory boards for Juno Therapeutics, Sapience, Roche, Tocagen, and BTG International. HK received compensation for serving on the advisory board for Roivant Sciences, the steering committee for Medtronic, the deputy editor for JAMA Neurology, and research support from BMS and Roche. MC provided consultative services for Merck and received honorarium for speaking from Diazyme and Diadexus. MS received research funding from Amgen and Diadexus. PM received research funding from Amgen Inc. The other authors report nothing to disclose., (© 2019 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals, Inc on behalf of International Society on Thrombosis and Haemostasis.)

Objectives: This study examined the association between urinary albumin excretion and incident heart failure (HF) hospitalization., Background: Excess urinary albumin excretion is more strongly associated with incident stroke and coronary heart disease risk in black than in white individuals. Whether similar associations extend to HF is unclear., Methods: This study examined the associations between the urinary albumin-to-creatinine ratio (ACR) and incident hospitalization for HF overall in 24,433 REGARDS (Reasons for Geographic and Racial Differences in Stroke) study participants free of suspected HF at baseline; findings were stratified by race and HF subtype (preserved vs. reduced ejection fraction). Models were adjusted for sociodemographic, clinical, and laboratory variables including estimated glomerular filtration rate, and multiple imputation was used to account for missing covariate data., Results: After a median follow-up of 9.2 years, 881 incident HF events (332 preserved ejection fraction, 447 reduced ejection fraction, 102 unspecified) were observed. Compared to the lowest ACR category (<10 mg/g), the risk of incident HF increased with increasing ACR categories (10 to 29 mg/g hazard ratio [HR]: 1.49; 95% confidence interval [CI]: 1.26 to 1.78; 30 to 300 mg/g HR: 2.32; 95% CI: 1.93 to 2.78; >300 mg/g HR: 4.42; 95% CI: 3.36 to 5.83) in the fully adjusted model. Results did not differ by race. The magnitude of the association between ACR and HF with preserved ejection fraction was greater than with HF with reduced ejection fraction (HR comparing highest vs. lowest ACR category: 6.20; 95% CI: 4.15 to 9.26 vs. HR: 4.37; 95% CI: 3.00 to 6.25, respectively; p = 0.05)., Conclusions: Higher ACR was associated with greater risk of incident HF hospitalization in community-dwelling black and white adults., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Patients with cystic fibrosis (CF) have increased risk of vitamin D deficiency owing to fat malabsorption and other factors. Vitamin D deficiency has been associated with increased risk of pulmonary exacerbations of CF., Objectives: The primary objective of this study was to examine the impact of a single high-dose bolus of vitamin D3 followed by maintenance treatment given to adults with CF during an acute pulmonary exacerbation on future recurrence of pulmonary exacerbations., Methods: This was a multicenter, double-blind, placebo-controlled, intent-to-treat clinical trial. Subjects with CF were randomly assigned to oral vitamin D3 given as a single dose of 250,000 International Units (IU) or to placebo within 72 h of hospital admission for an acute pulmonary exacerbation, followed by 50,000 IU of vitamin D3 or an identically matched placebo pill taken orally every other week starting at 3 mo after random assignment. The primary outcome was the composite endpoint of the time to next pulmonary exacerbation or death within 1 y. The secondary outcomes included circulating concentrations of the antimicrobial peptide cathelicidin and recovery of lung function as assessed by the percentage of predicted forced expiratory volume in 1 s (FEV1%)., Results: A total of 91 subjects were enrolled in the study. There were no differences between the vitamin D3 and placebo groups in time to next pulmonary exacerbation or death at 1 y. In addition, there were no differences in serial recovery of lung function after pulmonary exacerbation by FEV1% or in serial concentrations of plasma cathelicidin., Conclusions: Vitamin D3 initially given at the time of pulmonary exacerbation of CF did not alter the time to the next pulmonary exacerbation, 12-mo mortality, serial lung function, or serial plasma cathelicidin concentrations. This trial was registered at clinicaltrials.gov as NCT01426256., (© 2019 American Society for Nutrition.)

Background: Whether smoking increases the risk of atrial fibrillation (AF) remains debatable due to inconsistent reports., Methods: We examined the association between smoking and incident AF in 11,047 participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, one of the largest biracial, population-based cohort studies in the USA. Baseline (2003-2007) cigarette smoking status and amount (pack-years) were self-reported. Incident AF was determined by electrocardiography and history of a prior physician diagnosis at a follow-up examination conducted after a median of 10.6 years., Results: During follow-up, 954 incident AF cases were identified; 9.5% in smokers vs. 7.8% in non-smokers; p<0.001. In a model adjusted for socio-demographics, smoking (ever vs. never) was associated with a 15% increased risk of AF [OR (95%CI): 1.15(1.00, 1.31)], but this association was no longer significant after further adjustment for cardiovascular risk factors [OR (95% CI): 1.12 (0.97, 1.29)]. However, heterogeneities in the association were observed among subgroups; the association was stronger in young vs. old participants [OR (95%CI): 1.31 (1.03, 1.67) vs. 0.99 (0.83-1.18) respectively; interaction p-value=0.005] and in those with vs. without prior cardiovascular disease [OR (95%CI): 1.18 (0.90, 1.56) vs. 1.06 (0.90, 1.25) respectively; interaction p-value 0.0307]. Also, the association was significant in blacks but not in whites [OR (95%CI): 1.51 (1.12, 2.05) vs. 0.99 (0.84, 1.16), respectively], but the interaction p-value did not reach statistical significance (interaction p-value=0.65)., Conclusions: The association between smoking and AF is possibly mediated by a higher prevalence of cardiovascular risk factors in smokers, but there is marked heterogeneity in the strength of this association among subgroups which may explain the conflicting results in prior studies., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

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

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., Competing Interests: 2 Author disclosures: ME Goetz, SE Judd, TJ Hartman, W McClellan, A Anderson, and V Vaccarino, no conflicts of interest., (© 2016 American Society for Nutrition.)

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 self-identified 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., (© 2016 American Society for Nutrition.)

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., (© 2015 American Society for Nutrition.)

Obesity is associated with chronic kidney disease progression. Whether metabolic risk factors modify this association is unclear. Here we examined associations of body mass index (BMI) and metabolic health with risk of end-stage renal disease (ESRD) in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Among 21,840 participants eligible for analysis, 247 developed ESRD (mean follow-up of 6.3 years). Metabolic health significantly modified the association of BMI with ESRD. In models stratified by the presence or absence of the metabolic syndrome and adjusted for demographic, lifestyle, and clinical factors, higher BMI was associated with lower risk of ESRD in those without (hazard ratio per 5 kg/m2 increase in BMI 0.70, 95% CI 0.52, 0.95) but not those with (hazard ratio, 1.06) the metabolic syndrome. In models stratified by weight and metabolic health, compared with normal weight (BMI 18.5-24.9 kg/m2) participants without the metabolic syndrome the overweight individuals (BMI 25-29.9) and obese individuals (BMI of 30 or more) with the metabolic syndrome had greater risk of ESRD (hazard ratios of 2.03 and 2.29, respectively), whereas obesity without the metabolic syndrome was associated with lower risk of ESRD (hazard ratio 0.47). Thus, higher BMI is associated with lower ESRD risk in those without but not those with the metabolic syndrome.

Background: Metabolically healthy obesity may confer lower risk of adverse health outcomes compared with abnormal obesity. Diet and race are postulated to influence the phenotype, but their roles and their interrelations on healthy obesity are unclear., Objective: We evaluated food intakes of metabolically healthy obese women in comparison to intakes of their metabolically healthy normal-weight and metabolically abnormal obese counterparts., Methods: This was a cross-sectional study in 6964 women of the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Participants were aged 45-98 y with a body mass index (BMI; kg/m(2)) ≥18.5 and free of cardiovascular diseases, diabetes, and cancer. Food intake was collected by using a food-frequency questionnaire. BMI phenotypes were defined by using metabolic syndrome (MetS) and homeostasis model assessment of insulin resistance (HOMA-IR) criteria. Mean differences in food intakes among BMI phenotypes were compared by using ANCOVA., Results: Approximately one-half of obese women (white: 45%; black: 55%) as defined by MetS criteria and approximately one-quarter of obese women (white: 28%; black: 24%) defined on the basis of HOMA-IR values were metabolically healthy. In age-adjusted analyses, healthy obesity and normal weight as defined by both criteria were associated with lower intakes of sugar-sweetened beverages compared with abnormal obesity among both white and black women (P < 0.05). HOMA-IR-defined healthy obesity and normal weight were also associated with higher fruit and low-fat dairy intakes compared with abnormal obesity in white women (P < 0.05). Results were attenuated and became nonsignificant in multivariable-adjusted models that additionally adjusted for BMI, marital status, residential region, education, annual income, alcohol intake, multivitamin use, cigarette smoking status, physical activity, television viewing, high-sensitivity C-reactive protein, menopausal status, hormone therapy, and food intakes., Conclusions: Healthy obesity was not associated with a healthier diet. Prospective studies on relations of dietary patterns, which may be a better indicator of usual diet, with the phenotype would be beneficial., (© 2014 American Society for Nutrition.)

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.

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-deficiency 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.

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.

Background: Among obese adults, sodium intake has been associated with cardiovascular disease. Few data are available on sodium intake and albuminuria, a marker of kidney damage and risk factor for cardiovascular disease., Objective: We examined the relation between dietary sodium and potassium intakes and the ratio of sodium to potassium (Na/K) with albuminuria by BMI in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study (n = 30,239 adults aged ≥45 y)., Design: A modified Block 98 food-frequency questionnaire was used for dietary assessment in 21,636 participants, and nutritional variables were categorized by sex-specific quintiles. Normal weight, overweight, and obese were defined as BMI (in kg/m(2)) categories of 18.5-24.9, 25-29.9, and ≥30, respectively. Albuminuria was defined as a ratio (mg/g) of urinary albumin to creatinine of ≥30., Results: The prevalences of albuminuria were 11.5%, 11.6%, and 16.0% in normal-weight, overweight, and obese participants, respectively. The multivariable-adjusted ORs for albuminuria in a comparison of the highest with the lowest quintile of Na/K intake (≥1.12 to <0.70 for men and ≥1.07 to <0.62 for women) were 0.89 (95% CI: 0.65, 1.22), 1.08 (95% CI: 0.85, 1.36), and 1.28 (95% CI: 1.02, 1.61) in normal-weight, overweight, and obese participants, respectively. The highest quintile of dietary sodium was associated with an increased OR for albuminuria in obese participants (OR: 1.44; 95% CI: 1.00, 2.07) but not in normal-weight or overweight participants. Dietary potassium was not associated with albuminuria., Conclusion: In obese adults, higher dietary Na/K and sodium intakes were associated with albuminuria.

Vitamin D is an important prohormone for optimal intestinal calcium absorption for mineralization of bone. Because the vitamin D receptor is present in multiple tissues, there has been interest in evaluating other potential functions of vitamin D, particularly, in cardiovascular diseases (CVD). Cross-sectional studies have reported that vitamin D deficiency is associated with increased risk of CVD, including hypertension, heart failure, and ischemic heart disease. Initial prospective studies have also demonstrated that vitamin D deficiency increases the risk of developing incident hypertension or sudden cardiac death in individuals with preexisting CVD. Very few prospective clinical studies have been conducted to examine the effect of vitamin D supplementation on cardiovascular outcomes. The mechanism for how vitamin D may improve CVD outcomes remains obscure; however, potential hypotheses include the downregulation of the renin-angiotensin-aldosterone system, direct effects on the heart, and vasculature or improvement of glycemic control. This review will examine the epidemiologic and clinical evidence for vitamin D deficiency as a cardiovascular risk factor and explore potential mechanisms for the cardioprotective effect of vitamin D.

Background: The prevalences of both hypertension and vitamin D insufficiency are high in the United States. Recent clinical trials and animal studies have suggested that vitamin D insufficiency may be associated with elevated blood pressure., Objective: With cross-sectional data, we sought to determine whether vitamin D concentrations were related to systolic blood pressure (SBP) in the third National Health and Nutrition Examination Survey (1988-1992)., Design: Blood pressure was classified with 5 categories from the Joint National Committee 7 with a sixth category added to distinguish participants with normotensive SBP (<110 mm Hg) from those with high-normal SBP (110-119 mm Hg). We used predicted marginals to estimate the conditional means of serum 25 hydroxyvitamin D [25(OH)D] and to test for trend across blood pressure categories. We used linear regression to explore the association between vitamin D, blood pressure, and age., Results: Lower 25(OH)D concentrations were associated with a higher blood pressure category in whites (P<0.001); however, when controlling for age, the association was no longer significant. Concentrations of 25(OH)D>80 nmol/L decreased the age-related increase in SBP by 20% compared with participants having 25(OH)D concentrations<50 nmol/L (P<0.001). Only 8% of blacks had 25(OH)D concentrations>80 nmol/L., Conclusions: SBP is inversely associated with serum vitamin D concentrations in nonhypertensive white persons in the United States. This observation provides a rationale for studies on the potential effects of vitamin D supplementation as a method to reduce SBP in persons at risk of hypertension.