Racial Differences In Stroke Research Articles

Factor VIII and Incident Hypertension in Black and White Adults: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort.

Nearly half of all Americans have hypertension, and Black adults experience a disproportionate burden. Hypercoagulability may relate to hypertension risk, and higher levels of factor VIII increase thrombosis risk. Black adults have higher factor VIII and more hypertension than other groups. Whether higher factor VIII associates with incident hypertension is unknown. The Biomarkers as Mediators of Racial Disparities in Risk Factors (BioMedioR) study measured certain biomarkers in a sex-race stratified sample of 4,400 REGARDS participants who attended both visits. We included BioMedioR participants, excluding those with prevalent hypertension, missing factor VIII level, or covariates of interest. Modified Poisson regression estimated risk ratios (RR) for incident hypertension by higher log-transformed factor VIII level per SD (SD of log-transformed factor VIII, 0.33). Weighting was applied to take advantage of REGARDS sampling design. Among the 1,814 participants included (55% female, 24% Black race), the median follow-up was 9.5 years and 35% (2,146/6,138) developed hypertension. Black participants had a higher median (IQR) factor VIII level (105.6%; 87.1%-126.9%) than White participants (95.6%; 79.8%-115.9%; P < 0.001). The age- and sex-adjusted Black-White hypertension RR was 1.45 (95% CI 1.28, 1.63). Higher factor VIII was not associated with more hypertension (final model RR 1.01; 95% CI 0.94, 1.07). In a prospective study of Black and White adults without prevalent hypertension, factor VIII was not associated with greater hypertension risk.

Racial Differences in Ischemic and Hemorrhagic Stroke: An Ecological Epidemiological Study.

This study aimed to evaluate racial differences in the incidence of stroke by conducting an ecological epidemiological study using UK Biobank and Korean nationwide data. This study used individual data from the Korean National Health Insurance Service-Health Screening and UK Biobank, which included participants who underwent health examinations between 2006 and 2010. We included 112,750 East Asians (50.7% men, mean age: 52.6 years) and 210,995 Caucasians (44.7% men, mean age: 55.0 years) who were not diagnosed with atrial fibrillation, cardiovascular diseases, chronic kidney disease, chronic obstructive pulmonary disease, or cancer. The primary outcome was defined as a composite of ischemic and hemorrhagic stroke. East Asians tended to have a lower body mass index (23.7 vs. 26.4 kg/m2, p < 0.001) and a higher proportion of participants who did not engage in moderate-to-vigorous physical activity (49.6% vs. 10.7%, p < 0.001) than Caucasians. During the follow-up, East Asians had higher 5-year incidence rates (presented as per 1,000 person-years) for primary outcome (1.73 vs. 0.50; IR ratio [IRR]: 3.48, 95% confidence interval [CI]: 3.13-3.88), ischemic stroke (1.23 vs. 0.33; IRR: 3.70, 95% CI: 3.25-4.21), hemorrhagic stroke (0.56 vs. 0.18; IRR: 3.20, 95% CI: 2.67-3.84), and atrial fibrillation-related stroke (0.19 vs. 0.09; IRR: 2.04, 95% CI: 1.55-2.68). Based on this ecological epidemiological study, racial differences in stroke incidence were robust to a variety of statistical analyses, regardless of the subtype. This suggests the need for region-specific approaches to stroke prevention.

Sleep Apnea and Incident Stroke in a National Cohort of Black and White Adults.

Racial/ethnic differences have been documented in the relationship between obstructive sleep apnea (OSA) and stroke incidence, yet racial differences in OSA symptoms or treatment and their relationship with stroke incidence are underexplored and may contribute to stroke disparities. We comprehensively examined OSA symptoms and their relationships to stroke incidence by race/ethnicity. Data were collected from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a population-based cohort of Black and White individuals in the United States. Participants free from a stroke diagnosis at baseline were included. Participants self-reported the following: (1) snoring; (2) daytime sleepiness; (3) provider-diagnosed sleep apnea (PDSA); and (4) treatment for PDSA using positive airway pressure (PAP). OSA risk was categorized as high or low based on the Berlin Sleep Questionnaire. Incident stroke was defined as first occurrence of stroke over an average of 12 (SD 3.9) years of follow-up. We report the relationships between snoring, OSA risk, PDSA, PAP therapy use, and incident stroke by race/ethnicity using Cox proportional hazards models after adjusting for demographic and socioeconomic factors and stroke risk factors. Among the 22,192 participants (mean age [SD] 64.2[9.1] years), 38.1% identified as Black. Overall, snoring was not associated with incident stroke (hazard ratio [HR] 0.98, 95% CI 0.85-1.13). However, among White individuals but not Black individuals, high OSA risk and PDSA were associated with incident stroke (HR 1.22, 95% CI 1.01-1.47; HR 1.33, 95% CI 1.04-1.70, respectively). PAP therapy use among those with PDSA (compared with non-PDSA) was associated with incident stroke in White individuals (HR 1.38, 95% CI 1.05-1.80). PAP therapy use among those with PDSA (compared with those with PDSA without PAP therapy use) was associated with reduced risk of incident stroke in Black (HR 0.39, 95% CI 0.17-0.91) but not White (HR 0.63, 95% CI 0.37-1.10) individuals. White individuals with high OSA risk and those with PDSA with or without PAP therapy use were at increased incident stroke risk, whereas Black individuals reporting PDSA and PAP had reduced incident stroke risk relative to those not using PAP. Future research is needed to understand the mechanisms underlying racial differences in OSA and stroke such as differences in assessment modes and treatment.

Abstract P291: Understanding Participant Perspectives Towards the Formation of a National Participant Advisory Board Within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study: A Qualitative Study

Introduction: While participant advisory boards (PABs) are common among public health initiatives and clinical trials, they are less common among national, epidemiologic cohort studies. PABs could add value to researchers and participants alike, but their formation and functioning in this context is less understood. We aimed to elicit the perspectives of participants from the national REasons for Geographic and Racial Differences in Stroke (REGARDS) Study towards the formation of a PAB, which can inform future efforts to form one for this cohort study and others like it. Methods: REGARDS is a national prospective cohort study that enrolled &gt;30,000 Black and White community-dwelling adults aged ≥45 years from 48 states 2003-2007. Enrollment and follow-up is ongoing and done through mail and telephone. We used a convenience sampling approach to recruit from a subset of participants who responded to a newsletter about joining a PAB. Participants completed a one-on-one telephone or Zoom-based interview with study staff following a semi-structured interview guide. Interviews were recorded and professionally transcribed. Data were organized with NVivo software. Informed by the Cargo and Mercer’s Health Equity Research Practice Framework for Academic-Community Partnerships, we conducted a thematic analysis. Each transcript was independently coded by two team members, then reconciled by a third. Major themes and subthemes were identified. Results: The 18 participants had a median age of 69 years, 67% were women, 39% were Black, and 78% had a college degree or higher. Overall, participants were enthusiastic about the PAB and were inclined to meet as a group regularly via Zoom or telephone. Four key themes emerged: (1) The PAB should form and function with a core set of principles, including: trust, diversity, mutual respect, and accountability; of these, diversity was most important; (2) The PAB should not only inform studies (i.e. research questions, methodology), but also assist with the dissemination of science to diverse networks; (3) A formal process is required to form and maintain the PAB, as well as keeping members engaged; (4) Core values influenced participants’ willingness to serve on the PAB; they included internal motivation, the desire to translate knowledge into action, and social and environmental justice. Conclusion: This study highlights a willingness of participants in large epidemiologic cohort to participate in a PAB. Our results can inform the formation of a PAB in the REGARDS Study, and may be important for other observational cohorts interested in including participants in an advisory capacity.

Abstract 06: Residential Segregation and Thrombo-Inflammatory Biomarkers Related to Hypertension in Black and White Americans

Background: Thrombo-inflammation is involved in hypertension pathogenesis. Black people have higher thrombo-inflammatory biomarkers and hypertension burden than White people. It is unclear whether residential segregation, a driver of health inequities, has a differential impact on thrombo-inflammation in Black and White Americans. Hypothesis: Higher residential segregation is associated with adverse levels of thrombo-inflammatory biomarkers, and this association is greater among Black relative to White adults. Methods: This cross-sectional study included 4,362 participants of the biracial REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. County-level segregation was measured with the (1) dissimilarity index (DI, the difference in racial distribution of census tracts relative to their county), (2) isolation index (ISI, the degree to which Black people are exposed only to one another in a county), and (3) interaction index (ITI, the degree to which Black people are exposed to White people in a county). Linear regression was used to assess correlations of residential segregation indices with 7 thrombo-inflammatory biomarkers associated with hypertension risk: C-reactive protein (CRP), D-dimer, E-selectin, Factor IX, interferon (IFN)-γ, interleukin (IL)-6, and tumor necrosis factor (TNF)-α. Results: Worse ISI, ITI, and DI were associated with adverse levels of most biomarkers even with Bonferroni adjustment (Table). For example, CRP was 12% (95% CI: 9-16%) higher per SD higher ISI, 5%(95% CI: 1- 8%) higher per SD higher DI, and 9% (95% CI: 6-12%) higher per SD lower ITI. None of the associations differed significantly by race (p race* residential segregation index &gt;0.1). Conclusions: Several thrombo-inflammatory biomarkers important in hypertension were more adverse with greater residential segregation by three metrics, regardless of race. This indicates that residential segregation, a manifestation of structural racism, may become embodied in thrombo-inflammatory processes.

Abstract P426: County-Level Structural Racism and Diabetes Prevalence Among White and Black US Adults

Background: Diabetes Mellitus affects 12.7% non-Hispanic Black adults as opposed to 7% non-Hispanic White Adults. We hypothesized that higher structural racism (SR) is associated with greater diabetes prevalence among Black and White adults. Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study recruited 30,239 US Black and White adults from 48 contiguous US states in 2003-2007. We linked a novel county-level structural racism (CSR) metric reflecting domains of housing dissimilarity, school dissimilarity, high school graduation, incarceration, poverty, primary care access, and ambulatory care access. CSR was determined linked to REGARDS participants’ county location at time of recruitment. Diabetes was defined as fasting blood glucose ≥126 mg/dL or random blood glucose ≥200 mg/dL or use of diabetes medications. We excluded those missing CSR score and diabetes status. Poisson regression estimated relative risk (RR) of prevalent diabetes by higher (more adverse) CSR. Results: Among the 28,329 included participants (mean [SD] age 65 years, [9.43], 55% female participants, 42% Black participants). There was a greater proportion of Black adults in areas with higher CSR. As is shown in Table 1 , higher CSR was associated with higher RR of prevalent diabetes overall. However, higher CSR was associated with lower RR in race stratified models. Conclusions: Adverse levels of CSR were associated with lower diabetes prevalence in Black adults. It is unclear if this observation reflects operationalization of CSR, omitted variable bias, survival bias, or a true structural racism-diabetes association. Table 1 - Relative risk (RR) of Diabetes Prevalence age and sex adjusted per 1-point higher CSR*

Abstract P328: Hepatocyte Growth Factor and Incident Cognitive Impairment: The Reasons for Geographic and Racial Differences in Stroke (REGARDS)

Background: Cognitive impairment is a major public health burden in the U.S., and Black adults experience a disproportionate burden of cognitive impairment, including dementia. Hepatocyte growth factor (HGF) is a tyrosine kinase receptor MET agonist with neuroprotective properties, including peptide synthesis, neuronal regeneration, and inflammation reduction. Recombinant HGF aids endothelial repair and combats tissue fibrosis in mice. A positive HGF/MET pathway modulator (fosgonimeton) is in Phase 2 clinical trials for mild to moderate Alzheimer’s disease. We investigated the link between circulating HGF and incident cognitive impairment (ICI) in a national cohort study. Methods: REGARDS enrolled a cohort of 30,239 Black and White adults aged ≥45 in 2003-2007. ICI was identified using a 3-test battery administered every 2 years. Excluding participants with baseline cognitive impairment or stroke, with a mean follow-up of 3.5 years, 432 ICI cases and 520 controls were identified and HGF was measured in their baseline blood samples. Logistic regression estimated odds ratios (OR) of ICI by continuous HGF and also per quartile of HGF, controlling for known confounders. We assessed sex*HGF and race*HGF interactions on ICI. Restricted Cubic (RC) splines illustrated potential non-linear relationships. Results: Higher HGF was not associated with greater ICI risk in any model ( Figure ). There was no observed significant sex*HGF (P=0.58) or race*HGF interactions (P=0.19). RC splines visualized a possible non-linear relationship between lower HGF and higher risk of ICI relative to the median HGF level. Conclusions: In a prospective study of HGF in adults free from stroke or cognitive impairment, there was no clear association between higher HGF and ICI, though possible nonlinear associations might exist at low levels. This suggests that pharmaceuticals augmenting HGF pathways may benefit in primary prevention of ICI. Confirmatory studies are needed.

Abstract P320: Soluble Receptor for Advanced Glycation End Products and Incident Hypertension: REasons for Geographic And Racial Differences in Stroke (REGARDS)

Background: Black US adults experience greater hypertension burden than other groups and have lower levels of serum soluble receptor for advanced glycation end products (sRAGE). Higher sRAGE may dampen inflammation pathway activity. Inflammation is a hypertension risk factor. It is unclear if lower sRAGE is associated with greater risk of incident hypertension overall and among Black adults. Objective: To estimate the risk of incident hypertension by sRAGE level. Methods: REGARDS enrolled 30,239 Black and White adults in the 48 contiguous United States in 2003-07; a second visit occurred 2013-16. ELISAs measured sRAGE in 4,400 REGARDS participants who attended both visits. This analysis included participants with sRAGE levels and no prevalent hypertension. Hypertension was defined as BP ≥140/90 mm Hg or use of antihypertensive medications. Poisson regression estimated relative risk (RR) of incident hypertension by serum sRAGE quartiles in models adjusting for known confounders. Results: Among the 1803 participants (mean (SD] age 62 [8] years, 55% Women, 25% Black race) incident hypertension occurred in 35% (46% Black and 32% White participants). Median (IQR) sRAGE was 1114 pg/ml (206 to 4256) in Black and 1600 pg/ml (380 to 5500) in White adults. Models were stratified by race because of an sRAGE*race interaction on incident hypertension. Higher sRAGE was associated with lower hypertension risk in White participants in all models ( Table ). There was no association between sRAGE and hypertension in Black adults. Conclusions: Higher serum sRAGE was associated with lower hypertension risk in White, but not Black, adults when adjusted for known risk factors. Whether modifying sRAGE affects hypertension risk is unclear.

Abstract P491: Functional Annotations for Improvements in Height and Blood Pressure Polygenic Risk Scores

Background: Genome-wide association studies (GWAS) have advanced our understanding of the polygenic basis of common, complex disorders. However, translating GWAS findings into clinical applications remains challenging. Polygenic risk scores (PRS) hold promise for clinical use with recent methodologies enhancing predictive accuracy. This study compared two PRS (LDpred-funct which incorporates functional annotations into the score and a traditional linear scoring system) for traits with varying heritability in European- (EA) and African-ancestry (AA) populations, addressing a need to evaluate novel approaches across diverse conditions and populations. Hypothesis: This study hypothesized that integrating functional annotations into PRS derivation will enhance performance compared to assessing the genetic load for a trait. The addition will provide improvement for (1) traits with high (height) compared to moderate (systolic blood pressure, SBP) heritability and (2) individuals with EA relative to AA. Methods: This study used multi-ancestry summary statistics representing data from 4,080,687 individuals for height (GIANT consortium) and 436,099 individuals for SBP adjusted for antihypertensive medication use (UK Biobank). Two PRS for these traits were constructed using LDpred-funct: PRS funct which incorporates the functional annotation and PRS raw which is a simple linear scoring system. Optimization was performed in 8,916 AA and 1,716 EA participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. PRS predictive performance was evaluated by calculating the proportion of trait variance explained by the PRS (R 2 ) after accounting for age, sex, and genetic ancestry. Results: For height, the PRS funct outperformed PRS raw among both race groups, with a greater improvement among EA (PRS funct R 2 =0.110 versus PRS raw R 2 =0.060, 5% difference) compared to AA (PRS funct R 2 =0.042 versus PRS raw R 2 =0.034, 0.8% difference). Similar findings were observed for medication-adjusted SBP, where PRS funct had better predictive performance than PRS raw , and with greater improvement observed in the EA (PRS funct R 2 =0.042 versus PRS raw R 2 =0.027, 1.5% difference) compared to AA participants (PRS funct R 2 =0.014 versus PRS raw R 2 =0.010, 0.4% difference). Conclusions: Incorporating functional priors into the PRS enhanced the predictive accuracy for both traits. A greater improvement was observed for the higher heritability (height) versus the moderate heritability (SBP) trait, as well as within individuals of EA compared to AA. These findings are currently undergoing validation, using data from the Electronic Medical Records and Genomics (eMERGE) Network, highlighting the potential of incorporating functional annotations into PRS development for broader clinical applications.

Plasma Metabolites and Life's Simple 7 in REGARDS.

The American Heart Association's Life's Simple 7 (LS7) is a health metric that captures important factors associated with cardiovascular and cerebrovascular health. Previous studies highlight the potential of plasma metabolites to serve as a marker for lifestyle and health behavior that could be a target for stroke prevention. The objectives of this study were to identify metabolites that were associated with LS7 and incident ischemic stroke and mediate the relationship between the two. Targeted metabolomic profiling of 162 metabolites by liquid chromatography-tandem mass spectrometry was used to identify candidate metabolites in a stroke case-cohort nested within the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Weighted linear regression and weighted Cox proportional hazard models were used to identify metabolites that were associated with LS7 and incident ischemic stroke, respectively. Effect measures were based on a 1-SD change in metabolite level. Metabolite mediators were examined using inverse odds ratio weighting mediation analysis. The study comprised 1075 ischemic stroke cases and 968 participants in the random cohort sample. Three out of 162 metabolites were associated with the overall LS7 score including guanosine (β, -0.46 [95% CI, -0.65 to -0.27]; P=2.87×10-6), cotinine (β, -0.49 [95% CI, -0.70 to -0.28]; P=7.74×10-6), and acetylneuraminic acid (β, -0.59 [95% CI, -0.77 to -0.42]; P=4.29×10-11). Guanosine (hazard ratio, 1.47 [95% CI, 1.31-1.65]; P=6.97×10-11), cotinine (hazard ratio, 1.30 [95% CI, 1.16-1.44]; P=2.09×10-6), and acetylneuraminic acid (hazard ratio, 1.29 [95% CI, 1.15-1.45]; P=9.24×10-6) were associated with incident ischemic stroke. The mediation analysis identified guanosine (27% mediation, indirect effect; P=0.002), cotinine (30% mediation, indirect effect; P=0.004), and acetylneurminic acid (22% mediation, indirect effect; P=0.041) partially mediated the relationship between LS7 and ischemic stroke. We identified guanosine, cotinine, and acetylneuraminic acid that were associated with LS7, incident ischemic stroke, and mediated the relationship between LS7 and ischemic stroke.

Ambulatory Care Fragmentation and Total Health Care Costs.

The magnitude of the relationship between ambulatory care fragmentation and subsequent total health care costs is unclear. To determine the association between ambulatory care fragmentation and total health care costs. Longitudinal analysis of 15 years of data (2004-2018) from the national Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, linked to Medicare fee-for-service claims. A total of 13,680 Medicare beneficiaries who are 65 years and older. We measured ambulatory care fragmentation in each calendar year, defining high fragmentation as a reversed Bice-Boxerman Index ≥0.85 and low as <0.85. We used generalized linear models to determine the association between ambulatory care fragmentation in 1 year and total Medicare expenditures (costs) in the following year, adjusting for baseline demographic and clinical characteristics, a time-varying comorbidity index, and accounting for geographic variation in reimbursement and inflation. The average participant was 70.9 years old; approximately half (53%) were women. One-fourth (26%) of participants had high fragmentation in the first year of observation. Those participants had a median of 9 visits to 6 providers, with the most frequently seen provider accounting for 29% of visits. By contrast, participants with low fragmentation had a median of 8 visits to 3 providers, with the most frequently seen provider accounting for 50% of visits. High fragmentation was associated with $1085 more in total adjusted costs per person per year (95% CI $713 to $1457) than low fragmentation. Highly fragmented ambulatory care in 1 year is independently associated with higher total costs the following year.

Association Between Pharmacy Proximity With Cardiovascular Medication Use and Risk Factor Control in the United States.

Poor neighborhood-level access to health care, including community pharmacies, contributes to cardiovascular disparities in the United States. The authors quantified the association between pharmacy proximity, antihypertensive and statin use, and blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) among a large, diverse US cohort. A cross-sectional analysis of Black and White participants in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study during 2013 to 2016 was conducted. The authors designated pharmacy proximity by census tract using road network analysis with population-weighted centroids within a 10-minute drive time, with 5- and 20-minute sensitivity analyses. Pill bottle review measured medication use, and BP and LDL-C were assessed using standard methods. Poisson regression was used to quantify the association between pharmacy proximity with medication use and BP control, and linear regression for LDL-C. Among 16 150 REGARDS participants between 2013 and 2016, 8319 (51.5%) and 8569 (53.1%) had an indication for antihypertensive and statin medication, respectively, and pharmacy proximity data. The authors did not find a consistent association between living in a census tract with higher pharmacy proximity and antihypertensive medication use, BP control, or statin medication use and LDL-C levels, regardless of whether the area was rural, suburban, or urban. Results were similar among the 5- and 20-minute drive-time analyses. Living in a low pharmacy proximity census tract may be associated with antihypertensive and statin medication use, or with BP control and LDL-C levels. Although, in this US cohort, outcomes were similar for adults living in high or low pharmacy proximity census tracts.

Cardiometabolic Disease Staging and Major Adverse Cardiovascular Event Prediction in 2 Prospective Cohorts

BackgroundCardiometabolic risk prediction models that incorporate metabolic syndrome traits to predict cardiovascular outcomes may help identify high-risk populations early in the progression of cardiometabolic disease. ObjectivesThe purpose of this study was to examine whether a modified cardiometabolic disease staging (CMDS) system, a validated diabetes prediction model, predicts major adverse cardiovascular events (MACE). MethodsWe developed a predictive model using data accessible in clinical practice [fasting glucose, blood pressure, body mass index, cholesterol, triglycerides, smoking status, diabetes status, hypertension medication use] from the REGARDS (REasons for Geographic And Racial Differences in Stroke) study to predict MACE [cardiovascular death, nonfatal myocardial infarction, and/or nonfatal stroke]. Predictive performance was assessed using receiver operating characteristic curves, mean squared errors, misclassification, and area under the curve (AUC) statistics. ResultsAmong 20,234 REGARDS participants with no history of stroke or myocardial infarction (mean age 64 ± 9.3 years, 58% female, 41% non-Hispanic Black, and 18% diabetes), 2,695 developed incident MACE (13.3%) during a median 10-year follow-up. The CMDS development model in REGARDS for MACE had an AUC of 0.721. Our CMDS model performed similarly to both the ACC/AHA 10-year risk estimate (AUC 0.721 vs 0.716) and the Framingham risk score (AUC 0.673). ConclusionsThe CMDS predicted the onset of MACE with good predictive ability and performed similarly or better than 2 commonly known cardiovascular disease prediction risk tools. These data underscore the importance of insulin resistance as a cardiovascular disease risk factor and that CMDS can be used to identify individuals at high risk for progression to cardiovascular disease.

Neighborhood Disadvantage and Risk of Heart Failure: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

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. 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. 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. 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 63: Ultra-Processed Food Intake Predicts Stroke Risk in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Introduction: Higher intake of ultra-processed foods (UPFs) is linked to cardiometabolic diseases and adverse neurological outcomes, such as stroke and cognitive decline. However, it is controversial whether food processing confers neurological risk independent of nutritive information. We explored associations between UPFs and incident stroke in the longitudinal REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Methods: The NOVA system was used to classify items from a baseline food frequency questionnaire (FFQ) according to level of processing. Intake in grams for each NOVA category was normalized to total grams consumed. Scores quantifying adherence to other diets considered neuroprotective—including a Mediterranean, DASH, and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet—were also derived from FFQ data. Multivariable Cox models were used to evaluate associations between diet patterns and stroke. Results: The cohort included 15,656 participants with reliable dietary intake data and without a previous stroke. Greater intake of UPFs (NOVA4) was associated with increased stroke risk (HR per SD: 1.10, 95% CI [1.03-1.18], p=4.77x10 -3 ) in a model adjusted for demographic factors (age, race, sex, age-by-race interaction) and vascular risk factors (smoking, atrial fibrillation, hypertension, diabetes mellitus, cardiovascular disease, left ventricular hypertrophy). Intake of unprocessed or minimally processed foods (NOVA1) was associated with decreased stroke risk (HR: 0.87, 95% CI [0.81-0.93], p=5.56x10 -5 ) as was adherence to the Mediterranean, DASH, and MIND diets. Adding intake of NOVA1 or NOVA4 items to multivariable models that included other diet patterns resulted in improved model fit (greater log-partial-likelihood). In contrast, adding other dietary patterns to models that included NOVA1 or NOVA4 intake did not improve model fit. While associations between NOVA1 and NOVA4 intake and stroke persisted in models that included the Mediterranean, DASH, or MIND diets, associations between other diet patterns and stroke were not significant. Conclusion: Intake of differentially processed foods is associated with stroke risk independent of adherence to other dietary patterns.

Abstract TP13: Association Between Education Level and Post-Stroke Cognitive Decline - A Pooled Cohort Analysis of Four Cohorts

Introduction: We evaluated whether education level is associated with post-stroke cognitive decline and whether age modifies the association. Methods: We analyzed pooled data from 2,019 stroke survivors from the Atherosclerosis Risk in Communities, REasons for Geographic and Racial Differences in Stroke, Cardiovascular Health, and Framingham Offspring studies from 1971-2019. Participants ≥18 years with incident stroke and free of dementia were included (52% female and 39% Black). Repeated cognitive tests were administered in person or by telephone by trained cohort staff. Linear mixed-effects models were used to examine the association between education (less than high school, completed high school, some college, college graduate or more) and post-stroke cognitive decline for global cognition (primary outcome), executive function, and memory harmonized across cohorts and to examine effect modification by age. Median (IQR) follow-up was 4.1 (1.8, 7.2) years. Results: Compared to those with less than a high school education (n=339), stroke survivors with some college education (n=484) and stroke survivors with a college degree or more (n=583) had higher first post-stroke cognitive scores (Models M1a, M1b, and M1c, Table). Having some college education was associated with slower post-stroke decline in global cognition (Model M1a) compared to those with less than a high school education. Having some college education or a college degree was associated with faster post-stroke decline in executive function (Model M1b, Table) compared to those with less than a high school education. Significant interactions by age were lacking for all outcomes. Conclusions: Higher education level was associated with higher initial post-stroke cognitive scores, slower decline in global cognition, and faster decline in executive function, regardless of age. Stroke might narrow the gap in executive function between stroke survivors with higher and lower education.

Abstract 72: Association Between Stroke Subtype and Post-Stroke Cognitive Decline: A Pooled Cohort Analysis of Four Cohorts

Introduction: Associations between stroke subtype and post-stroke cognitive decline are unclear. We determined if post-stroke cognitive trajectories differed between 1) hemorrhagic vs. ischemic stroke and 2) ischemic stroke subtypes. Methods: We identified 1,150 eligible dementia-free individuals with incident stroke (93% ischemic, 7% hemorrhagic, 50% women, 31% Black, median age, 65) from 4 cohort studies from 1971-2019: Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Offspring Study, and Reasons for Geographic and Racial Differences in Stroke. Of the ischemic strokes, 22% were small-vessel occlusion, 8% large artery atherosclerosis, 21% cardioembolic, and 49% cryptogenic/other determined etiology. Linear mixed-effects models were used to estimate longitudinal changes in cognition after incident stroke. Global cognition (primary outcome), executive function, and memory were harmonized across studies and standardized as T-scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Median (IQR) follow-up was 5.9 (3.2, 9.2) years. Results: Survivors of ischemic stroke had significant declines in global cognition, executive function, and memory (Table). For example, global cognition declined -0.35 points/year (95%CI, -0.43, -0.26); P &lt;0.001. Initial post-stroke cognitive scores and post-stroke cognitive trajectories did not differ between hemorrhagic and ischemic stroke, except for lower initial post-stroke memory scores (adjusted difference, -1.39 points; 95% CI, -2.77, -0.01; P =0.049). Survivors of small-vessel occlusions had significant declines in global cognition, executive function, and memory (Table). Initial post-stroke cognitive scores and post-stroke cognitive trajectories did not differ by ischemic stroke subtype. Conclusions: Our results suggest that stroke survivors experience long-term post-stroke cognitive decline regardless of subtype.

Abstract WP236: Harmonization of Stroke Risk Prediction Variables Using Natural Language Processing

Introduction: Early identification of stroke risk can profoundly influence an individual's chance of survival. While machine learning-based stroke risk prediction models perform better than traditional counterparts, they require integrating diverse open data sources. Variable discrepancies - where the same concept is described differently - pose challenges for data integration, requiring time-intensive manual harmonization. To address this, we developed an automated harmonization technique using natural language models. Methods: We utilized data from the Atherosclerosis Risk in Communities (ARIC), Multi-Ethnic Study of Atherosclerosis (MESA), Framingham Offspring Study, and Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohorts. Our approach involved training a two-layer fully connected neural network (FCN) to predict a harmonized ‘concept variable’ based on variable descriptions. These predictions employed embeddings from Bidirectional Encoder Representations from Transformers for Biomedical Text Mining (BioBERT). Further refining was achieved through paired sentence classification tasks to determine if description pairs shared identical concepts. We experimented with both separate cohort training and combined cohort training to evaluate context dependency. We used cosine similarity between the embeddings of the pre-trained BioBERT encoder as a prediction score for our baseline method. Results: The harmonization methods using natural language models outperformed the baseline method. The FCN model improved the area under the receiver operating characteristic from 0.787 (baseline) to 0.985 for the paired classification task. For harmonization concept prediction, the top-2 accuracy - correct prediction in the top two answers - improved from 11.9% (baseline) to 54.6%, while the top-5 accuracy improved from 16.1% (baseline) to 67.6%. Conclusions: Utilizing natural language processing for data harmonization provides a scalable approach that improves accuracy and efficiency of prediction. This facilitates the inclusion of diverse cohorts, broadening the sample size and range of indicators available, which in turn advances the versatility and the generalizability of stroke risk prediction models.

Abstract TMP97: Temporal Trends in Black-White Differences of Antihypertensive Treatment in Individuals With and Without History of Stroke: Reasons for Geographic and Racial Differences in Stroke (REGARDS)

Introduction: In 2014, the Eighth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC8) included race-specific recommendations for antihypertensive treatments (e.g. calcium channel blockers [CCBs] for Black persons). The impact of these guidelines on anti-hypertensive regimen changes over time, and if this varied by prevalent stroke status, is unclear. Methods: REGARDS participants reporting anti-hypertensive medications with and without history of stroke who completed an in-home examination in 2003-2007 (Visit 1) or 2013-2016 (Visit 2) were included. Logistic regression mixed models estimated odds ratios (OR) and 95% confidence intervals (CI) for use of each antihypertensive class for Visit 2 vs. Visit 1 and Black vs. White with interaction by prevalent stroke status, adjusted for demographic and socioeconomic status. Results: Of 17,222 participants without prevalent stroke at Visit 1, Black participants had greater odds of ACE-inhibitor usage relative to White participants (OR 1.68, 95% CI 1.44-1.95). This difference remained but was smaller in 7,476 participants without stroke at Visit 2 (OR 1.29, CI 1.20-1.38). In participants without prevalent stroke, lower odds of CCB usage among Black compared to White participants was observed at Visit 1 (OR 0.47, CI 0.41-0.55) but there was no difference at Visit 2 (OR 1.00, CI 0.94-1.07). Among 1,436 participants with prevalent stroke at Visit 1, Black participants had lower odds of CCB use compared to White participants (OR 0.48, CI 0.29-0.82) but similar odds in 689 participants with prevalent stroke at Visit 2 (OR 1.15, CI 0.91-1.44). Conclusions: Consistent with JNC8 recommendations for first-line medication administration in Black persons with hypertension, there was a higher likelihood of CCB use over time among Black participants in REGARDS. Adherence to race-based guidance for antihypertensive medication may be increasing over time.

Serum zinc concentration and dietary zinc intake in relation to cognitive function: an analysis of the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.

There are several pathways by which zinc may be a modifiable factor to slow age-related cognitive decline. We investigated the associations between serum and dietary zinc and cognitive impairment in a longitudinal cohort. We used data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort (n = 30,239) and the REGARDS Trace Element Study (n = 2666). Baseline serum zinc concentrations (2003-2007) were measured using inductively coupled plasma mass spectrometry. Baseline dietary zinc intake was measured via the Block food frequency questionnaire. Serum zinc concentrations and dietary zinc intake were categorized into quartiles. The outcome of interest was impairment on the Six-Item Screener (SIS), a measure of global cognitive functioning administered annually. The Enhanced Cognitive Battery (ECB), a more comprehensive series of tests assessing memory and fluency, was administered every two years and considered a secondary outcome. Associations between zinc and incident impairment were assessed using multivariable logistic regression. Among 2065 participants with serum zinc data, 184 individuals developed impairment over 10years of follow-up. In adjusted models, there was no significant association between serum zinc and impairment as assessed by the SIS or the ECB. Among 18,103 participants who had dietary data, 1424 experienced incident impairment on the SIS. Dietary zinc intake was not significantly associated with impairment as assessed by the SIS or the ECB in adjusted models. Findings from this U.S. cohort did not support the hypothesis that serum zinc concentration or dietary zinc intake is associated with the risk of cognitive impairment.