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BACKGROUND: Hypertension is a highly prevalent cardiovascular disease risk factor that may be related to inflammation. Whether adverse levels of specific inflammatory cytokines relate to hypertension is unknown. The present study sought to determine whether higher levels of IL (interleukin)-1β, IL-6, TNF (tumor necrosis factor)-α, IFN (interferon)-γ, IL-17A, and CRP (C-reactive protein) are associated with a greater risk of incident hypertension. METHODS: The REGARDS study (Reasons for Geographic and Racial Difference in Stroke) is a prospective cohort study that recruited 30 239 community-dwelling Black and White adults from the contiguous United States in 2003 to 2007 (visit 1), with follow-up 9 years later in 2013 to 2016 (visit 2). We included participants without prevalent hypertension who attended follow-up 9 years later and had available laboratory measures and covariates of interest. Poisson regression estimated the risk ratio of incident hypertension by level of inflammatory biomarkers. RESULTS: Among 1866 included participants (mean [SD] aged of 62 [8] years, 25% Black participants, 55% women), 36% developed hypertension. In fully adjusted models comparing the third to first tertile of each biomarker, there was a greater risk of incident hypertension for higher IL-1β among White (1.24 [95% CI, 1.01–1.53]) but not Black participants (1.01 [95% CI, 0.83–1.23]) and higher TNF-α (1.20 [95% CI, 1.02–1.41]) and IFN-γ (1.22 [95% CI, 1.04–1.42]) among all participants. There was no increased risk with IL-6, IL-17A, or CRP. CONCLUSIONS: Higher levels of IL-1β, TNF-α, and IFN-γ, representing distinct inflammatory pathways, are elevated in advance of hypertension development. Whether modifying these cytokines will reduce incident hypertension is unknown. [ABSTRACT FROM AUTHOR]

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

Background: 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]

Background: The Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) diet (high in nuts, seeds, vegetables, berries and low in meat, dairy, and butter) has been associated with reduced risk of dementia. However, no studies have examined the role of the MIND diet in a racially diverse population nor have there been studies that have examined the association of the MIND diet with dementia mortality. Method: We examined data from Black and White adults (age 45‐98) in the US‐based REGARDS cohort. Dietary and covariate data were collected at baseline (2002‐2007). MIND diet score was created as described by other cohort studies (Table footnote). The primary outcome was dementia‐related mortality through December 31, 2020 from the National Death Index using ICD‐10 codes F00‐F03, G30, G31.0‐G31.1, and R54. Cox proportional hazards regression was used to model MIND diet score (in tertiles and as a continuous variable) and time to dementia death. To ensure robust association across sub‐groups, we tested for interactions of MIND diet with sex, race, age, obesity, history of stroke, and baseline cognitive impairment and adjusted for competing risks. Result: A total of 18,277 participants (mean age 64.9) had dietary data available to calculate the MIND diet score. MIND diet score was higher among females compared with males, White compared with Black participants, and college graduates. There were no differences in accordance by age. After a median of 12 years, participants with the highest MIND diet scores had the lowest risk of dementia death HR = 0.78 {95% CI; (0.66, 0.94)} comparing the 3rd tertile with the 1st tertile and after adjustment for age, race, sex, income, education, total energy, and other medical conditions (Table). This association was attenuated slightly when a competing risk analysis was considered HR = 0.84 {95%CI; (0.70, 1.00)}. There were no significant interactions observed. Conclusion: The MIND diet score is associated with dementia death in a large bi‐racial cohort in the US. This association is robust across race, age, and sex groups. Dietary interventions using the MIND diet may further clarify whether this association is causal and whether MIND diet may be an important tool in reducing rates of dementia. [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: Heart failure (HF) affects >6 million US adults, with recent increases in HF hospitalizations. We aimed to investigate the association between neighborhood disadvantage and incident HF events and potential differences by diabetes status. METHODS: We included 23 645 participants from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke), a prospective cohort of Black and White adults aged ≥45 years living in the continental United States (baseline 2005–2007). Neighborhood disadvantage was assessed using a Z score of 6 census tract variables (2000 US Census) and categorized as quartiles. Incident HF hospitalizations or HF-related deaths through 2017 were adjudicated. Multivariable-adjusted Cox regression was used to examine the association between neighborhood disadvantage and incident HF. Heterogeneity by diabetes was assessed using an interaction term. RESULTS: The mean age was 64.4 years, 39.5% were Black adults, 54.9% females, and 18.8% had diabetes. During a median follow-up of 10.7 years, there were 1125 incident HF events with an incidence rate of 3.3 (quartile 1), 4.7 (quartile 2), 5.2 (quartile 3), and 6.0 (quartile 4) per 1000 person-years. Compared to adults living in the most advantaged neighborhoods (quartile 1), those living in neighborhoods in quartiles 2, 3, and 4 (most disadvantaged) had 1.30 (95% CI, 1.06–1.60), 1.36 (95% CI, 1.11–1.66), and 1.45 (95% CI, 1.18–1.79) times greater hazard of incident HF even after accounting for known confounders. This association did not significantly differ by diabetes status (interaction P =0.59). For adults with diabetes, the adjusted incident HF hazards comparing those in quartile 4 versus quartile 1 was 1.34 (95% CI, 0.92–1.96), and it was 1.50 (95% CI, 1.16–1.94) for adults without diabetes. CONCLUSIONS: In this large contemporaneous prospective cohort, neighborhood disadvantage was associated with an increased risk of incident HF events. This increase in HF risk did not differ by diabetes status. Addressing social, economic, and structural factors at the neighborhood level may impact HF prevention. [ABSTRACT FROM AUTHOR]

Achieving optimal cardiovascular health in rural populations can be challenging for several reasons including decreased access to care with limited availability of imaging modalities, specialist physicians, and other important health care team members. Therefore, innovative solutions are needed to optimize health care and address cardiovascular health disparities in rural areas. Mobile examination units can bring imaging technology to underserved or remote communities with limited access to health care services. Mobile examination units can be equipped with a wide array of assessment tools and multiple imaging modalities such as computed tomography scanning and echocardiography. The detailed structural assessment of cardiovascular and lung pathology, as well as the detection of extracardiac pathology afforded by computed tomography imaging combined with the functional and hemodynamic assessments acquired by echocardiography, yield deep phenotyping of heart and lung disease for populations historically underrepresented in epidemiological studies. Moreover, by bringing the mobile examination unit to local communities, innovative approaches are now possible including engagement with local professionals to perform these imaging assessments, thereby augmenting local expertise and experience. However, several challenges exist before mobile examination unit–based examinations can be effectively integrated into the rural health care setting including standardizing acquisition protocols, maintaining consistent image quality, and addressing ethical and privacy considerations. Herein, we discuss the potential importance of cardiac multimodality imaging to improve cardiovascular health in rural regions, outline the emerging experience in this field, highlight important current challenges, and offer solutions based on our experience in the RURAL (Risk Underlying Rural Areas Longitudinal) cohort study. [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 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--PCSK9 loss-of-function (LOF) variants allow for the examination of the effects of lifetime reduced lowdensity lipoprotein cholesterol (LDL-C) on cardiovascular events. We examined the association of PCSK9 LOF variants with LDL-C and incident coronary heart disease and stroke through a meta-analysis of data from 8 observational cohorts and 1 randomized trial of statin therapy. Methods and Results--These 9 studies together included 17 459 blacks with 403 (2.3%) having at least 1 Y142X or C679X variant and 31 306 whites with 955 (3.1%) having at least 1 R46L variant. Unadjusted odds ratios for associations between PCSK9 LOF variants and incident coronary heart disease (851 events in blacks and 2662 events in whites) and stroke (523 events in blacks and 1660 events in whites) were calculated using pooled Mantel-Haenszel estimates with continuity correction factors. Pooling results across studies using fixed-effects inverse-variance-weighted models, PCSK9 LOF variants were associated with 35 mg/dL (95% confidence interval [CI], 32-39) lower LDL-C in blacks and 13 mg/dL (95% CI, 11-16) lower LDL-C in whites. PCSK9 LOF variants were associated with a pooled odds ratio for coronary heart disease of 0.51 (95% CI, 0.28-0.92) in blacks and 0.82 (95% CI, 0.63-1.06) in whites. PCSK9 LOF variants were not associated with incident stroke (odds ratio, 0.84; 95% CI, 0.48-1.47 in blacks and odds ratio, 1.06; 95% CI, 0.80-1.41 in whites). Conclusions--PCSK9 LOF variants were associated with lower LDL-C and coronary heart disease incidence. PCSK9 LOF variants were not associated with stroke risk. [ABSTRACT FROM AUTHOR]