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Background: Individual inflammation biomarkers are associated with incident coronary heart disease (CHD) events. However, there is limited research on whether the risk for incident CHD is progressively higher with a higher number of inflammation biomarkers in abnormal levels.Methods: We used data from 15,758 Reasons for Geographic and Racial Differences in Stroke (REGARDS) study participants aged ≥45 years without a history of CHD at baseline in 2003-2007. Abnormal levels of baseline high-sensitivity C-reactive protein, leukocyte count and serum albumin were defined as ≥3.8 mg/L (3rd tertile), ≥6.3 x 109 cells/L (3rd tertile), and <4.0 g/dL (1st tertile), respectively. The outcome was a composite of incident myocardial infarction or CHD death.Results: Overall, 38.9% (n = 6,123) had 0, 36.6% (n = 5,774) had 1, 19.8% (n = 3,113) had 2 and 4.7% (n = 748) had 3 biomarkers of inflammation in abnormal levels. Over a median follow-up of 11.4 years, 954 (6.1%) participants had incident CHD. The rate of incident CHD per 1000 person-years for individuals with 0, 1, 2, and 3 biomarkers of inflammation in abnormal levels was 4.4 (95% confidence interval [CI]: 3.9-5.0), 6.3 (95% CI: 5.6-6.9), 8.8 (95% CI: 7.8-9.9), and 10.6 (95% CI: 8.1-13.1), respectively. Multi-variable adjusted hazard ratios for incident CHD associated with 1, 2 and 3 versus no inflammation biomarker in abnormal levels were 1.26 (95% CI: 1.07-1.49), 1.72 (95% CI: 1.43-2.07), and 1.84 (95% CI: 1.37-2.47), respectively (P-trend < .001).Conclusions: The number of inflammation markers in abnormal levels was associated with increased risk of incident CHD after multi-variable adjustment. [ABSTRACT FROM AUTHOR]

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. We used prospective cohort design to complete time-to-event analyses. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Background: The Dietary Approaches to Stop Hypertension (DASH) diet pattern has shown some promise for preventing heart failure (HF), but studies have been conflicting.Objective: To determine whether the DASH diet pattern was associated with incident HF in a large biracial and geographically diverse population.Methods and Results: Among participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study of adults aged ≥45 years who were free of suspected HF at baseline in 2003-2007, the DASH diet score was derived from the baseline food frequency questionnaire. The main outcome was incident HF defined as the first adjudicated HF hospitalization or HF death through December 31, 2016. We estimated hazard ratios for the associations of DASH diet score quartiles with incident HF, and incident HF with reduced ejection fraction and HF with preserved ejection fraction using the Lunn-McNeil extension to the Cox model. We tested for several prespecified interactions, including with age. Compared with the lowest quartile, individuals in the second to fourth DASH diet score quartiles had a lower risk for incident HF after adjustment for sociodemographic and health characteristics: quartile 2 hazard ratio, 0.69 (95% confidence interval [CI], 0.56-0.85); quartile 3 hazard ratio, 0.71 (95% CI, 0.58-0.87); and quartile 4 hazard ratio, 0.73 (95% CI, 0.58-0.92). When stratifying results by age, quartiles 2-4 had a lower hazard for incident HF among those age <65 years, quartiles 3-4 had a lower hazard among those age 65-74, and the quartiles had similar hazard among those age ≥75 years (Pinteraction = .003). We did not find a difference in the association of DASH diet with incident HF with reduced ejection fraction vs HF with preserved ejection fraction (P = .11).Conclusions: DASH diet adherence was inversely associated with incident HF, specifically among individuals <75 years old. [ABSTRACT FROM AUTHOR]

To investigate the longitudinal association between magnesium (Mg) intake and the risk of metabolic syndrome (MetS). 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. 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. 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. [ABSTRACT FROM AUTHOR]

Several cohort studies have found associations between long-term exposure to air pollution and stroke risk. However, it is unclear whether the surrounding ecology may modify these associations. This study evaluates associations of air pollution with stroke risk by ecoregions, which are areas of similar type, quality, and quantity of environmental resources in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. We assessed the incidence of stroke in 26,792 participants (45+ yrs) from the REGARDS study, a prospective cohort recruited across the contiguous United States. One-yr and 3-yr means of PM 2.5 , PM 10 , O 3 , NO 2 , SO 2 , and CO were estimated at baseline using data from the Center for Air, Climate, & Energy Solution, and assigned to participants at the census block group level. Incident stroke was ascertained through September 30, 2020. Relations of air pollutants with the risk of incident stroke were estimated using Cox proportional hazards models, adjusting for relevant demographics, behavioral risk factors, and neighborhood urbanicity. Models were stratified by EPA designated ecoregions. A 5.4 μg/m3 (interquartile range) increase in 1-yr PM 10 was associated with a hazard ratio (95 %CI) for incident stroke of 1.07 (1.003, 1.15) in the overall study population. We did not find evidence of positive associations for PM 2.5 , O 3 , NO 2 , SO 2 , and CO in the fully adjusted models. In our ecoregion-specific analysis, associations of PM 2.5 with stroke were stronger in the Great Plains ecoregion (HR = 1.44) than other ecoregions, while associations for PM 10 were strongest in the Eastern Temperate Forests region (HR = 1.15). The associations between long-term exposure to air pollution and risk of stroke varied by ecoregion. Our results suggests that the type, quality, and quantity of the surrounding ecology can modify the effects of air pollution on risk of stroke. [Display omitted] • Long-term PM 10 concentrations were positively related to stroke risk. • PM effects were significantly modified by the ecological region of participants. • Associations of PM 2.5 on stroke were strongest in the Great Plains. • Urbanicity modified the relations between air pollution and stroke risk. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (Pinteraction > .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. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 m2, the adjusted risk of SCD was significantly elevated only among those with eGFR <45 mL/min/1.73 m2 (HR 1.66, 95% CI 1.06-2.58). The subgroup with eGFR <45 mL/min/1.73 m2 (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 m2 who were at significantly increased SCD risk.Conclusion: Low levels of kidney injury as measured by ACR predict an increase in SCD risk. [ABSTRACT FROM AUTHOR]

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

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

Background: Stroke symptoms in the general adult population are common and associated with stroke risk factors, lower physical and mental functioning, impaired cognitive status, and future stroke. Our objective was to determine the association of stroke symptoms with self-reported hospitalization or emergency department (ED) visit.Methods: Lifetime history of stroke symptoms (sudden weakness, numbness, unilateral or general loss of vision, loss of ability to communicate or understand) was assessed at baseline in a national, population-based, longitudinal cohort study of 30,239 blacks and whites younger than 45 years, enrolled from 2003 to 2007. Self-reported hospitalization or ED visit and reason were collected during follow-up through March 2013. The symptom-hospitalization association was assessed by proportional hazards analysis in persons who were stroke/transient ischemic attack-free at baseline (27,126) with adjustment for sociodemographics and further adjustment for risk factors.Results: One or more stroke symptoms were reported by 4758 (17.5%). After adjustment for sociodemographics, stroke symptoms were most strongly associated with greater risk of hospitalization/ED for cardiovascular disease (CVD) (hazard ratio [HR] = 1.87, 95% confidence interval [CI]: 1.78-1.96), stroke (HR = 1.69, 95% CI: 1.55-1.85), and any reason (HR = 1.39, 95% CI: 1.34-1.44). These associations remained significant and only modestly reduced after risk factor adjustment.Conclusions: Stroke symptoms are a marker for future hospitalization and ED visit not only for stroke but also for CVD in general. Findings suggest a role for stroke symptom assessment as a novel and simple approach for identifying individuals at high risk for CVD including stroke in whom preventive strategies could be implemented. [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 We investigated the association between family history of stroke (FHS) and Life's Simple 7 (LS7), a public health metric defined by the American Heart Association. Methods Reasons for Geographic and Racial Differences in Stroke is a national population-based cohort of 30,239 blacks and whites, aged 45 years or older, sampled from the US population between 2003 and 2007. Data were collected by telephone, mail questionnaires, and in-home examinations. FHS was defined as any first-degree relative with stroke. Levels of the LS7 components (total cholesterol, blood pressure, fasting glucose, physical activity, diet, smoking, and body mass index) were each coded as poor (0 points), intermediate (1 point), or ideal (2 points) health. Ordinal logistic regression was used to model the data. Results Among 20,567 subjects with complete LS7 and FHS data, there were 7702 (37%) participants with an FHS. The mean age of the participants was 64 years. The mean (± standard deviation) overall LS7 score was lower for blacks (6.5 ± 2.0) than that of whites (7.6 ± 2.1). FHS was associated with poorer levels of physiological factors, particularly high blood pressure (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.07-1.19) and inversely associated with behaviors such as smoking (OR, .92; 95% CI, .85-.99). Conclusions Our results suggest that screening for FHS can provide an opportunity for earlier detection and management of modifiable risk factors. [ABSTRACT FROM AUTHOR]

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/m²) ≥ 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. [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]

Background: Stroke symptoms are common among people without a history of stroke or transient ischemic attack; however, it is unknown if particular attention should be focused on specific symptoms for subgroups of patients. Methods: Using baseline data from 26,792 REasons for Geographic And Racial Differences in Stroke (REGARDS) participants without a history of transient ischemic attack or stroke, we assessed the association between age, sex, race, current smoking, hypertension, and diabetes and the 6 stroke symptoms in the Questionnaire for Verifying Stroke-Free Status. Results: The mean age of participants was 64.4 ± 9.4 years, 40.7% were black, and 55.2% were women. After multivariable adjustment, older persons more often reported an inability to understand (odds ratio [OR] 1.16 per 10 years older age; 95% confidence interval [CI] 1.07-1.25) and unilateral vision loss (OR 1.09; 95% CI 1.01-1.18) and less often reported numbness (OR 0.83; 95% CI 0.79-0.87) and weakness (OR 0.85; 95% CI 0.80-0.90). Women reported difficulty communicating more often than men (OR 1.36; 95% CI 1.19-1.56). The OR for blacks compared to whites for each of the 6 stroke symptoms was increased, markedly so for unilateral numbness (OR 1.97; 95% CI 1.81-2.16), unilateral weakness (OR 1.96; 95% CI 1.76-2.18), and inability to understand (OR 1.87; 95% CI 1.61-2.18). Current smoking, hypertension, and diabetes were associated with higher ORs for each stroke symptom. Conclusions: The association of risk factors with 6 individual stroke symptoms studied was not uniform, suggesting the need to emphasize individual stroke symptoms in stroke awareness campaigns when targeting populations defined by risk. [ABSTRACT FROM AUTHOR]

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/m2) categories of 18.5-24.9, 25-29.9, and ⩾30, respectively. Alburninuria 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, re- spectively. 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 ⩾l.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% Cl: 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 albuminui-ia in obese participants (OR: 1 .44; 95% CI: 1.00, 2.07) but not in normal-weight or overweight partic- ipants. Dietary potassium was not associated with albuminuria. Conclusion: In obese adults, higher dietary Na/K and sodium in- takes were associated with albuminuria. [ABSTRACT FROM AUTHOR]

BACKGROUND: Low adherence to antihypertensive medication is an important barrier to achieving blood pressure control. Few data are available for medication adherence in adults with chronic kidney disease (CKD). STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: 3,936 and 9,129 participants with and without CKD using antihypertensive medication in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study, respectively. CKD was defined as albuminuria with albumin excretion⩾30 mg/g or estimated glomerular filtration rate<60 mL/min/1.73 m2. OUTCOMES: Medication adherence and uncontrolled hypertension. MEASUREMENTS: Medication adherence was assessed using a validated 4-item scale. Blood pressure was measured 2 times by trained staff. RESULTS: In REGARDS participants with and without CKD, 1,426 (36.2%) and 2,421 (26.5%) had uncontrolled hypertension with blood pressure⩾140/90 mm Hg, and 2,656 (67.5%) and 5,627 (61.6%), ⩾130/80 mm Hg. Also, 27.7% of those with CKD and 27.9% of those without CKD responded "yes" to ever forgetting to take their medication and 4.4% and 4.2%, respectively, responded yes to being careless about taking their medication. Also, 5.7% and 5.3% responded yes to missing taking medication when they felt better, and 4.2% and 3.6%, to missing it when they felt sick. Overall, 23.3% and 23.7% of participants with and without CKD responded yes to 1 adherence question, whereas 7.7% and 7.2%, respectively, responded yes to 2 or more adherence questions. In those with CKD, the multivariable adjusted ORs for uncontrolled hypertension (blood pressure⩾140/90 mm Hg) for individuals answering yes to 1 and 2 or more versus 0 adherence questions were 1.26 (95% CI, 1.05-1.51) and 1.49 (95% CI, 1.12-1.98), respectively. Analogous ORs for systolic/diastolic blood pressure⩾130/80 mm Hg were 1.06 (95% CI, 0.78-1.45) and 1.20 (95% CI, 0.88-1.64). LIMITATIONS: Pharmacy fill data were not available. CONCLUSIONS: Individuals with CKD had similarly poor medication-taking behaviors as those without CKD. [ABSTRACT FROM AUTHOR]

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

Abstract: Vitamin D has been reported to lower blood pressure in vivo by regulating the renin-angiotensin system; however, there are limited clinical studies to support this finding in humans. We investigated the effect of vitamin D treatment on hypertension in a three-arm randomized placebo controlled pilot and feasibility study. We tested placebo with two forms of vitamin D: cholecalciferol (vitamin D3) and the active form of vitamin D, calcitriol. Subjects were recruited from the Atlanta Veterans Affairs Medical Center in Decatur, GA between April and August 2008. Subjects received 200,000IU of vitamin D3 (n =3) weekly for 3 weeks or matching placebo (n =3) weekly for 3 weeks (n =3) or 0.5μg calcitriol (n =2) taken twice daily for one week. Our primary endpoint was blood pressure measured by 24h ambulatory blood pressure monitor. Subjects receiving calcitriol experienced a 9% decrease in mean systolic blood pressure (SBP) compared placebo (p <0.001). One week after conclusion of calcitriol therapy SBP returned to pre-treatment levels. There was no reduction in blood pressure in the placebo or vitamin D3 groups. Results from this pilot study suggests that active vitamin D therapy may be an effective short-term intervention for reducing blood pressure and needs to be explored further in larger controlled studies. [ABSTRACT FROM AUTHOR]

To measure the association of baseline psychological symptoms (depressive symptoms and perceived stress) with withdrawal from a cohort study. 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. 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. Depressive symptoms were significantly associated with withdrawal. Prevalence of depressive symptoms at baseline is an important indicator of participant retention in large prospective cohorts. [ABSTRACT FROM AUTHOR]

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. 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. 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. Higher fasting GH was associated with higher risk of all-cause and cardiovascular mortality and improved risk prediction, regardless of sex or race. [Display omitted] • Elevated fasting growth hormone is associated with an increased risk of all-cause and cardiovascular mortality. • This association does not differ by sex or race. • Growth hormone may be a useful biomarker for risk stratifying individuals. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Post-stroke physical activity has widespread health benefits. Environmental exposures may shape post-stroke physical activity behavior. This study investigates the relationships between environmental exposures and post-stroke physical activity.Methods: Stroke survivors (n=374) from a cohort of Black and White adults with post-stroke accelerometer data (2009-2013) were eligible for this study. Participants' home addresses were linked with secondary data to capture environmental characteristics, including annual density of neighborhood resources (e.g., parks, physical activity facilities, and intellectual stimulation destinations), 2010 neighborhood SES, 2010 neighborhood crime, and daily information on extremely cold days. Post-stroke light physical activity and moderate-to-vigorous physical activity were captured using accelerometers over a 7-day period. Linear regression and 2-part/hurdle models were used to estimate the relationship between the density of neighborhood resources with light physical activity and with moderate-to-vigorous physical activity, respectively. Analyses were conducted in 2021.Results: A 10% increase in the number of extremely cold days was associated with 6.37 fewer minutes of daily light physical activity (95% CI= -11.37, -1.37). A 1-SD increase in neighborhood SES was associated with greater odds (OR=1.10, 95% CI=1.02, 1.19) of doing any moderate-to-vigorous physical activity. Among participants obtaining any moderate-to-vigorous physical activity, a 1-unit (count/km2) increase in destinations for intellectual stimulation was associated with 0.99 (95% CI=0.02, 1.97) more minutes of daily moderate-to-vigorous physical activity. All other environmental exposures were not associated with post-stroke light physical activity or moderate-to-vigorous physical activity.Conclusions: Environmental exposures may facilitate physical activity participation among stroke survivors. This study found that weather, neighborhood SES, and proximity to destinations for intellectual stimulation were associated with physical activity over and above individual factors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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/km2) 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. [ABSTRACT FROM AUTHOR]

The American South has been characterized as a Stroke Belt due to high cardiovascular mortality. We examine whether mortality rates and race differences in rates reflect birthplace exposure to Jim Crow-era inequalities associated with the Plantation South. The plantation mode of agricultural production was widespread through the 1950s when older adults of today, if exposed, were children. We use proportional hazards models to estimate all-cause mortality in Non-Hispanic Black and White birth cohorts (1920–1954) in a sample (N = 21,941) drawn from RE asons for G eographic and R acial D ifferences in S troke (REGARDS), a national study designed to investigate Stroke Belt risk. We link REGARDS data to two U.S. Plantation Censuses (1916, 1948) to develop county-level measures that capture the geographic overlap between the Stroke Belt, two subregions of the Plantation South, and a non-Plantation South subregion. Additionally, we examine the life course timing of geographic exposure: at birth, adulthood (survey enrollment baseline), neither, or both portions of life. We find mortality hazard rates higher for Black compared to White participants, regardless of birthplace, and for the southern-born compared to those not southern-born, regardless of race. Race-specific models adjusting for adult Stroke Belt residence find birthplace-mortality associations fully attenuated among White—except in one of two Plantation South subregions—but not among Black participants. Mortality hazard rates are highest among Black and White participants born in this one Plantation South subregion. The Black-White mortality differential is largest in this birthplace subregion as well. In this subregion, the legacy of pre-Civil War plantation production under enslavement was followed by high-productivity plantation farming under the southern Sharecropping System. • Most Black birth cohorts (pre-1960) were born in Southern Stroke Belt regions holding plantations. • We linked REGARDS data to U.S. Plantation Censuses to examine county-level birthplace exposures. • Proportional hazards models examined race differences in mortality associated with birthplace. • Birth in a plantation region with a legacy of pre-1860s enslavement most elevated mortality risk. • The racial gap in mortality was also largest among REGARDS participants born in this subregion. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. • Population studies have shown that black race is a natriuretic peptide (NP) deficiency state. • The effect of age, sex, body mass index (BMI) and estimated glomerular filtration rate (eGFR) on NP levels by race have not been described. • The relationship of N-terminal-pro-B-type NP (NT-proBNP) with age and sex was similar in both races. • The inverse relationship between NT-proBNP and BMI was linear among whites, while non-linear among blacks. • The non-linear inverse relationship of NT-proBNP with eGFR significantly differed by race. [ABSTRACT FROM AUTHOR]

Background: Dietary patterns and associations with incident heart failure (HF) are not well established in the United States.Objectives: The purpose of this study was to determine associations of 5 dietary patterns with incident HF hospitalizations among U.S. adults.Methods: The REGARDS (REasons for Geographic and Racial Differences in Stroke) trial is a prospective cohort of black and white adults followed from 2003 to 2007 through 2014. Inclusion criteria included completion of a food frequency questionnaire and no baseline coronary heart disease or HF. Five dietary patterns (convenience, plant-based, sweets, Southern, and alcohol/salads) were derived from principal component analysis. The primary endpoint was incident HF hospitalization.Results: This study included 16,068 participants (mean age 64.0 ± 9.1 years, 58.7% women, 33.6% black participants, 34.0% residents of the stroke belt). After a median of 8.7 years of follow-up, 363 participants had incident HF hospitalizations. Compared with the lowest quartile, the highest quartile of adherence to the plant-based dietary pattern was associated with a 41% lower risk of HF in multivariable-adjusted models (hazard ratio: 0.59; 95% confidence interval: 0.41 to 0.86; p = 0.004). Highest adherence to the Southern dietary pattern was associated with a 72% higher risk of HF after adjusting for age, sex, and race and for other potential confounders (education, income, region of residence, total energy intake, smoking, physical activity, and sodium intake; hazard ratio: 1.72; 95% confidence interval: 1.20 to 2.46; p = 0.005). However, the association was attenuated and no longer statistically significant after further adjusting for body mass index in kg/m2, waist circumference, hypertension, dyslipidemia, diabetes mellitus, atrial fibrillation, and chronic kidney disease. No statistically significant associations were observed with incident HF with reduced or preserved ejection fraction hospitalizations and the dietary patterns. No associations were observed with the other 3 dietary patterns.Conclusions: Adherence to a plant-based dietary pattern was inversely associated with incident HF risk, whereas the Southern dietary pattern was positively associated with incident HF risk. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Vitamin D and intact parathyroid hormone (iPTH) concentrations differ between individuals of African and European descent and may play a role in observed racial differences in bone mineral density (BMD). These findings suggest that mapping by admixture linkage disequilibrium (MALD) may be informative for identifying genetic variants contributing to these ethnic disparities. Admixture mapping was performed for serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, vitamin D-binding protein (VDBP), bioavailable vitamin D, and iPTH concentrations and computed tomography measured thoracic and lumbar vertebral volumetric BMD in 552 unrelated African Americans with type 2 diabetes from the African American—Diabetes Heart Study. Genotyping was performed using a custom Illumina ancestry informative marker (AIM) panel. For each AIM, the probability of inheriting 0, 1, or 2 copies of a European-derived allele was determined. Non-parametric linkage analysis was performed by testing for association between each AIM using these probabilities among phenotypes, accounting for global ancestry, age, and gender. Fine-mapping of MALD peaks was facilitated by genome-wide association study (GWAS) data. VDBP levels were significantly linked in proximity to the protein coding locus (rs7689609, LOD = 11.05). Two loci exhibited significant linkage signals for 1,25-dihydroxyvitamin D on 13q21.2 (rs1622710, LOD = 3.20) and 12q13.2 (rs11171526, LOD = 3.10). iPTH was significantly linked on 9q31.3 (rs7854368, LOD = 3.14). Fine-mapping with GWAS data revealed significant known (rs7041 with VDBP, P = 1.38 × 10 − 82 ) and novel (rs12741813 and rs10863774 with VDBP, P < 6.43 × 10 − 5 ) loci with plausible biological roles. Admixture mapping in combination with fine-mapping has focused efforts to identify loci contributing to ethnic differences in vitamin D-related traits. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is common in patients with life-threatening cancer and those undergoing active cancer treatment. However, data from subjects with a history of non-life-threatening cancer and those who do not require active cancer treatment are lacking. A total of 15,428 (mean age 66 ± 8.9 years; 47% women; 45% blacks) participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study with baseline data on previous cancer diagnosis and AF were included. Participants with life-threatening cancer and active cancer treatment within 2 years of study enrollment were excluded. History of cancer was identified using computer-assisted telephone interviews. AF cases were identified from baseline electrocardiogram data and by a self-reported history of a previous diagnosis. Logistic regression was used to examine the cross-sectional association between cancer diagnosis and AF. A total of 2,248 (15%) participants had a diagnosis of cancer and 1,295 (8.4%) had AF. In a multivariable logistic regression model adjusted for sociodemographic characteristics (age, gender, race, education, income, and region of residence) and cardiovascular risk factors (systolic blood pressure, high-density lipoprotein cholesterol, total cholesterol, C-reactive protein, body mass index, smoking, diabetes, antihypertensive and lipid-lowering agents, left ventricular hypertrophy, and cardiovascular disease), those with cancer were more likely to have prevalent AF than those without cancer (odds ratio 1.19, 95% confidence interval 1.02 to 1.38). Subgroup analyses by age, sex, race, cardiovascular disease, and C-reactive protein yielded similar results. In conclusion, AF was more prevalent in participants with a history of non-life-threatening cancer and those who did not require active cancer treatment in REGARDS. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine whether behavioral mechanisms explain the association between depressive symptoms and myocardial infarction (MI) or death in individuals with coronary heart disease (CHD). Background: Depressive symptoms are associated with increased morbidity and mortality in individuals with CHD, but it is unclear how much behavioral mechanisms contribute to this association. Methods: The study included 4,676 participants with a history of CHD. Elevated depressive symptoms were defined as scores ≥4 on the Center for Epidemiologic Studies Depression 4-item Scale. The primary outcome was definite/probable MI or death from any cause. Incremental proportional hazards models were constructed by adding demographic data, comorbidities, and medications and then 4 behavioral mechanisms (alcohol use, smoking, physical inactivity, and medication non-adherence). Results: At baseline, 638 (13.6%) participants had elevated depressive symptoms. Over a median 3.8 years of follow up, 125 of 638 (19.6%) participants with and 657 of 4,038 (16.3%) without elevated depressive symptoms had events. Higher risk of MI or death was observed for elevated depressive symptoms after adjusting for demographic data (hazard ratio [HR]: 1.41, 95% confidence interval [CI]: 1.15 to 1.72) but was no longer significant after adjusting for behavioral mechanisms (HR: 1.14, 95% CI: 0.93 to 1.40). The 4 behavioral mechanisms together significantly attenuated the risk for MI or death conveyed by elevated depressive symptoms (−36.9%, 95% CI: −18.9 to −119.1%), with smoking (−17.6%, 95% CI: −6.5% to −56.0%) and physical inactivity (−21.0%, 95% CI: −9.7% to −61.1%) having the biggest explanatory roles. Conclusions: Our findings suggest potential roles for behavioral interventions targeting smoking and physical inactivity in patients with CHD and comorbid depression. [ABSTRACT FROM AUTHOR]