Racial Differences In Stroke Research Articles

Cardiovascular Risk Factors and Genetic Risk in Transthyretin V142I Carriers.

Nearly 3% to 4% of Black individuals in the United States carry the transthyretin V142I variant, which increases their risk of heart failure. However, the role of cardiovascular (CV) risk factors (RFs) in influencing the risk of clinical outcomes among V142I variant carriers is unknown. This study aimed to assess the impact of CV RFs on the risk of heart failure in V142I carriers. This study included self-identified Black individuals without prevalent heart failure from 6 TOPMed (Trans-Omics for Precision Medicine) cohorts, the REGARDS (Reasons for Geographic And Racial Differences in Stroke) study, and the All of Us Research Program. The cohort was stratified based on the V142I genotype and the number of CV RFs (hypertension, diabetes, obesity, and hypercholesterolemia). Adjusted Cox models were used to assess the association of heart failure with the V142I genotype and CV RF profile, taking noncarriers with a favorable CV RF profile as reference. The cross-sectional analysis, including 1,625 V142I carriers among 48,365 Black individuals, found that the prevalence of CV RFs did not vary by V142I carrier status. In the longitudinal analysis, there were 587 (3.2%) V142I carriers among 18,407 Black individuals (median age: 60 years [Q1-Q3: 52-68 years], 63.0% female). Among carriers, the heart failure risk was attenuated with a favorable (0 or 1 RF) CV RF profile (adjusted HR: 2.26; 95%CI: 1.58-3.23) compared with an unfavorable (3 or 4 RFs) CV RF profile (adjusted HR: 4.14; 95%CI: 2.79-6.14). A favorable CV RF profile lowers but does not abrogate V142I variant-associated heart failure risk. This study highlights the importance of having a favorable CV RF profile among V142I carriers for risk reduction of heart failure.

The association of leptin and incident hypertension in the reasons for geographic and racial differences in stroke (REGARDS) cohort.

Leptin is an adipokine associated with obesity and with hypertension in animal models. Whether leptin is associated with hypertension independent of obesity is unclear. Relative to White adults, Black adults have higher circulating leptin concentration. As such, leptin may mediate some of the excess burden of incident hypertension among Black adults. REGARDS enrolled 30,239 adults aged ≥45 years from 48 US states in 2003-07. Baseline leptin was measured in a sex- and race-stratified sample of 4400 participants. Modified Poisson regression estimated relative risk (RR) of incident hypertension (new ≥140/≥90 mmHg threshold or use of antihypertensives) per SD of log-transformed leptin, stratified by obesity (BMI of 30 kg/m2). Inverse odds ratio weighting estimated the % mediation by leptin of the excess hypertension RR among Black relative to White participants. Among the 1821 participants without prevalent hypertension, 35% developed incident hypertension. Obesity modified the relationship between leptin and incident hypertension (P-interaction 0.006) such that higher leptin was associated with greater hypertension risk in the crude model among those with BMI < 30 kg/m2, but not those with BMI ≥ 30 kg/m2. This was fully attenuated when adjusting for anthropometric measures. In the crude model, Black adults had a 52% greater risk of incident hypertension. Leptin did not significantly mediate this disparity. In this national U.S. sample, leptin was associated with incident hypertension among non-obese but not obese adults. Future investigations should focus on the effect of weight modification on incident hypertension among non-obese adults with elevated leptin.

Associations among claims-based care fragmentation, self-reported gaps in care coordination, and self-reported adverse events

BackgroundFragmentation of care (that is, the use of multiple ambulatory providers without a dominant provider) may increase the risk of gaps in communication among providers. However, it is unclear whether people with fragmented care (as measured in claims) perceive more gaps in communication among their providers. It is also unclear whether people who perceive gaps in communication experience them as clinically significant (that is, whether they experience adverse events that they attribute to poor coordination).MethodsWe conducted a longitudinal study using data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, including a survey on perceptions of healthcare (2017–2018) and linked fee-for-service Medicare claims (for the 12 months prior to the survey) (N = 4,296). We estimated correlation coefficients to determine associations between claims-based and self-reported numbers of ambulatory visits and ambulatory providers. We then used logistic regression to determine associations between claims-based fragmentation (measured with the reversed Bice-Boxerman Index [rBBI]) and self-reported gaps in care coordination and, separately, between claims-based fragmentation and self-reported adverse events that the respondent attributed to poor coordination.ResultsThe correlation coefficient between claims-based and self-report was 0.37 for the number of visits and 0.38 for the number of providers (p < 0.0001 for each). Individuals with high fragmentation by claims (rBBI ≥ 0.85) had a 23% increased adjusted odds of reporting any gap in care coordination (95% CI 3%, 48%) and, separately, a 61% increased adjusted odds of reporting an adverse event that they attributed to poor coordination (95% CI 11%, 134%).ConclusionsMedicare beneficiaries with claims-based fragmentation also report gaps in communication among their providers. Moreover, these gaps appear to be clinically significant, with beneficiaries reporting adverse events that they attribute to poor coordination.

Trajectory of Cognitive Decline After Incident Heart Failure Hospitalization: Findings From the REGARDS Study.

Cognitive impairment is common among adults with heart failure (HF) and associated with poor outcomes. However, less is known about the trajectory of cognitive decline after a first HF hospitalization. We examined the rate of cognitive decline among adults with incident HF hospitalization compared with those without HF hospitalization. The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a prospective longitudinal study of 23 894 participants aged ≥45 years free of HF at baseline. HF hospitalization was expert adjudicated. Changes in global cognitive function (primary outcome) were assessed with the Six-Item Screener (range, 0-6). Secondary outcomes included change in Word List Learning (range, 0-30), Word List Delayed Recall (WLD; range, 0-10), and Animal Fluency Test (range, 0+). Segmented linear mixed-effects regression models were used. Over 5 years, mean scores across all 4 cognitive tests declined for all participants regardless of HF status. Those with incident HF hospitalization experienced faster declines in the Six-Item Screener versus those who were HF free (difference, -0.031 [95% CI, -0.047 to -0.016]; P<0.001), a finding that persisted in fully adjusted models. Those with incident HF hospitalization did not experience faster declines in Word List Learning, Word List Delayed Recall, or Animal Fluency Test scores compared with those without HF hospitalization. Participants with hospitalization for HF with preserved, compared with reduced, ejection fraction had faster decline in Animal Fluency Test. Global cognitive decline occurred faster among adults with incident HF hospitalization compared with those who remained free of HF hospitalization. This pattern was not seen for the other cognitive domains.

The Association Between Experienced Discrimination and Pain in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

The relationship between experienced discrimination and its effects on pain interference and management among racial disparities is not well explored. This research investigated these associations among Black and White U.S. adults. The analysis involved 9369 Black and White adults in the REasons for Geographic and Racial Differences in Stroke (REGARDS), assessing experiences of discrimination, pain interference (SF-12), and pain treatment, incorporating factors like demographics, comorbidities, and stress. Black participants experiencing moderate discrimination were found to have a 41% increased likelihood of pain interference (aOR 1.41, 95% CI 1.02-1.95), similaritythose facing high levels of discriminationalso showed a 41% increase (aOR 1.41, 95% CI 1.06-1.86) compared to those without such experiences. White individuals reporting moderate discrimination also faced a heightened risk, with a 21% greater chance of pain interference (aOR 1.21, 95% CI 1.01-1.45). Notably, the presence of moderate discrimination among Black participants correlated with a 12% reduced probability of receiving pain treatment (aOR 0.88, 95% CI 0.56-1.37). Furthermore, Black, and White individuals who reported discrimination when seeking employment had a 33% (aOR 0.67, 95% CI 0.45-0.98) and 32% (aOR 0.68, 95% CI 0.48-0.96) lower likelihood, respectively, of receiving treated pain. The study elucidates how discrimination exacerbates pain interference and restricts access to treatment, affecting Black and White individuals differently. These findings underscore an urgent need for strategies to counteract discrimination's negative effects on healthcare outcomes. Addressing these disparities is crucial for advancing health equity and improving the overall quality of care.

Race, social determinants of health, and comorbidity patterns among participants with heart failure in the REasons for geographic and racial differences in stroke (REGARDS) study

BackgroundAmong individuals with heart failure (HF), racial differences in comorbidities may be mediated by social determinants of health (SDOH).MethodsBlack and White US community-dwelling participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study aged ≥ 45 years with an adjudicated HF hospitalization between 2003 and 2017 were included in this cross-sectional analysis. We assessed whether higher prevalence of comorbidities in Black participants compared to White participants were mediated by SDOH in socioeconomic, environment/housing, social support, and healthcare access domains, using the inverse odds weighting method.ResultsBlack (n = 240) compared to White (n = 293) participants with HF with preserved ejection fraction (HFpEF) had higher prevalence of diabetes [1.38 (95% CI 1.18–1.61)], chronic kidney disease [1.21 (95% CI 1.01–1.45)], and anemia [1.33 (95% CI 1.02–1.75)] and lower prevalence of atrial fibrillation [0.80 (95% CI (0.65–0.98)]. Black (n = 314) compared to White (n = 367) participants with HF with reduced ejection fraction (HFrEF) had higher prevalence of hypertension [1.04 (95% CI 1.02–1.07)] and diabetes [1.26 (95% CI 1.09–1.45)] and lower prevalence of coronary artery disease [0.86 (95% CI 0.78–0.94)] and atrial fibrillation [0.70 (95% CI 0.58–0.83)]. Socioeconomic status explained 14.5%, 26.5% and 40% of excess diabetes, anemia, and chronic kidney disease among Black adults with HFpEF; however; mediation was not statistically significant and no other SDOH substantially mediated differences in comorbidity prevalence.ConclusionsSocioeconomic status partially mediated excess diabetes, anemia, and chronic kidney disease experienced by Black adults with HFpEF, but differences in other comorbidities were not explained by other SDOH examined.

Stroke Severity, Caregiver Feedback, and Cognition in the REGARDS-CARES Study.

Cognitive impairment after stroke is common and is present in up to 60% of survivors. Stroke severity, indicated by both volume and location, is the most consequential predictor of cognitive impairment, with severe strokes predicting higher chances of cognitive impairment. The current investigation examines the associations of 2 stroke severity ratings and a caregiver-report of poststroke functioning with longitudinal cognitive outcomes. One hundred fifty-seven caregivers and stroke survivor dyads participated in the CARES (Caring for Adults Recovering From the Effects of Stroke) project, an ancillary study of the REGARDS (Reasons for Geographic and Racial Differences in Stroke) national cohort study. The Glasgow Outcome Scale and modified Rankin Scale scores collected at hospitalization discharge were included as 2 primary predictors of cognitive impairment. The number of caregiver-reported problems and impairments at 9 months following stroke were included as a third predictor. Cognition was measured using a biennial telephone battery and included the domains of learning, memory, and executive functioning. Multiple cognitive assessments were analyzed up to 5 years poststroke, controlling for prestroke cognition and demographic variables of the stroke survivor. Separate mixed models showed significant main effects of the Glasgow Outcome Scale (b=0.3380 [95% CI, 0.14-0.5]; P=0.0009), modified Rankin Scale (b=-0.2119 [95% CI, -0.32 to -0.10]; P=0.0002), and caregiver-reported problems (b=-0.0671 [95% CI, -0.09 to -0.04]; P<0.0001) on longitudinal cognitive scores. In a combined model including all 3 predictors, only caregiver-reported problems significantly predicted cognition (b=-0.0480 [95% CI, -0.08 to -0.03]; P<0.0001). These findings emphasize the importance of caregiver feedback in predicting cognitive consequences of stroke.

Trends in Black-White Differences of Antihypertensive Treatment in Individuals With and Without History of Stroke.

Recent hypertension guidelines for the general population have included race-specific recommendations for antihypertensives, whereas current stroke-specific recommendations for antihypertensives do not vary by race. The impact of these guidelines on antihypertensive regimen changes over time, and if this has varied by prevalent stroke status, is unclear. The use of antihypertensive medications was studied cross-sectionally among self-identified Black and White participants, aged ≥45 years, with and without history of stroke, from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Participants completed an in-home examination in 2003-2007 (visit 1) with/without an examination in 2013-2016 (visit 2). Stratified by prevalent stroke status, logistic regression mixed models examined associations between antihypertensive class use for visit 2 versus visit 1 and Black versus White individuals with an interaction adjusted for demographics, socioeconomic status, and vascular risk factors/vital signs. Of 17 244 stroke-free participants at visit 1, Black participants had greater adjusted odds of angiotensin-converting enzyme inhibitor usage than White participants (odds ratio [OR], 1.51 [95% CI, 1.30-1.77]). This difference was smaller in the 7476 stroke-free participants at visit 2 (OR, 1.16 [95% CI, 1.08-1.25]). In stroke-free participants at visit 1, Black participants had lower odds of calcium channel blocker (CCB) usage than White participants (OR, 0.47 [95% CI, 0.41-0.55]), but CCB usage did not differ significantly between Black and White stroke-free participants at visit 2 (OR, 1.02 [95% CI, 0.95-1.09]). Among 1437 stroke survivor participants at visit 1, Black participants had lower odds of CCB use than White participants (OR, 0.34 [95% CI, 0.26-0.45]). In 689 stroke survivor participants at visit 2, CCB use did not differ between Black and White participants (OR, 0.80 [95% CI, 0.61-1.06]). Racial differences in the use of guideline-recommended antihypertensives decreased between 2003-2007 and 2013-2016 in stroke-free individuals. In stroke survivors, racial differences in CCB usage narrowed over the time periods. These findings suggest there is still a mismatch between race-specific hypertension guidelines and recent clinical practice.

Association Between Caregiver Strain and Self-Care Among Caregivers With Hypertension: Findings From the REGARDS Study.

Self-care for adults with hypertension includes adherence to lifestyle behaviors and medication. For unpaid caregivers with hypertension, the burden of family caregiving may adversely impact self-care. We examined the association between caregiver strain and hypertension self-care among caregivers with hypertension. We included participants of the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study who identified as caregivers and had hypertension. Caregiver strain, assessed by self-report, was categorized as "none/some" or "high." Hypertension self-care was assessed individually across 5 domains (Dietary Approaches to Stop Hypertension [DASH] diet, physical activity, alcohol use, cigarette smoking, and medication adherence) and a composite self-care score summing performance across them. The association between caregiver strain and hypertension self-care was examined with multivariable linear regression. Among the 2128 caregivers with hypertension, 18.1% reported high caregiver strain. Caregivers with high strain versus those with none/some were less adherent to the DASH diet (50.8% versus 38.9%, P<0.002), physically inactive (44.4% versus 36.2%, P<0.009), current smokers (19.7% versus 13.9%, P<0.004), and had lower overall self-care scores (6.6 [SD 1.7] versus 7.0 [SD 1.7], P<0.001). In an age-adjusted model, high caregiver strain was associated with worse hypertension self-care (β=-0.37 [95% CI, -0.61 to -0.13]); this remained significant but was reduced in magnitude after adjustment for sociodemographics (β=-0.35 [-0.59 to -0.11]), comorbidities (β=-0.34 [-0.57 to -0.10]), caregiving intensity (β=-0.34 [-0.59 to 0.10]), and psychological factors (β=-0.26 [-0.51 to 0.00]). High caregiver strain was associated with worse hypertension self-care overall and across individual domains. Increased awareness of caregiver strain and its potential impact on hypertension self-care is warranted.

Single-Ancestry versus Multi-Ancestry Polygenic Risk Scores for CKD in Black American Populations.

Chronic kidney disease (CKD) is a risk factor for cardiovascular disease and early death. Recently, polygenic risk scores (PRS) have been developed to quantify risk for CKD. However, African ancestry populations are underrepresented in both CKD genetic studies and PRS development overall. Moreover, European-ancestry derived PRS demonstrate diminished predictive performance in African ancestry populations. This study aimed to develop a PRS for CKD in Black Americans. We obtained score weights from a meta-analysis of genome-wide association studies (GWAS) for estimated glomerular filtration rate (eGFR) in the Million Veteran Program (MVP) and Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study to develop an eGFR PRS. We optimized the PRS risk model in a cohort of Participants from the Hypertension Genetic Epidemiology Network (HyperGEN). Validation was performed in subsets of Black participants of the Trans-Omics in Precision Medicine (TOPMed) Consortium and Genetics of Hypertension Associated Treatment (GenHAT) Study. The prevalence of CKD-defined as stage 3 or higher-was associated with the PRS as a continuous predictor (OR[95% CI]:1.35[1.08,1.68]) and in a threshold-dependent manner. Further, including APOL1 risk status-a putative variant for CKD with higher prevalence among those of sub-Saharan African descent-improved the score's accuracy. PRS associations were robust to sensitivity analyses accounting for traditional CKD risk factors, as well as CKD classification based on prior eGFR equations. Compared with previously published PRS, the predictive performance of our PRS was comparable to a European-ancestry derived PRS for kidney traits. However, both single-ancestry PRS were less predictive than multi-ancestry derived PRS. In this study, we developed a PRS that was significantly associated with CKD with improved predictive accuracy when including APOL1 risk status. However, PRS generated from multi-ancestry populations outperformed single-ancestry PRS in our study.

Social Determinants of Health and Cardiovascular Risk among Adults with Diabetes: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

Social determinants of health (SDOH) have been associated with diabetes risk; however, their association with cardiovascular disease (CVD) events in individuals with diabetes is poorly described. We hypothesized that a greater number of SDOH among individuals with diabetes would be associated with a higher risk of CVD events. The REasons for Geographic and Racial Differences in Stroke (REGARDS) study is a national, biracial cohort of 30,239 individuals ≥45 years old recruited in 2003-2007. We included 6,322 participants with diabetes at baseline, defined as healthcare professional diagnosis, diabetes medication use, or blood glucose values. Seven SDOH that were individually associated with CVD events were included (P<0.20). The outcome was CVD events, a composite of expert-adjudicated myocardial infarction, stroke, or cardiovascular death. We estimated Cox proportional hazard models to examine associations between number of SDOH (0, 1, 2, ≥3) and CVD events. In an age and sex adjusted model, the presence of multiple SDOH significantly increased the risk of any CVD event (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.26 to 1.74 for two SDOH; HR, 1.68; 95% CI, 1.43 to 1.96 for ≥3 SDOH). This finding was attenuated but remained statistically significant in a fully adjusted model (HR, 1.19; 95% CI, 1.01 to 1.40 for two SDOH; HR, 1.27; 95% CI, 1.07 to 1.50 for ≥3 SDOH). Having multiple SDOH was independently associated with an increased risk of CVD events, a finding driven by cardiovascular death. Identifying individuals with diabetes who have multiple SDOH may be helpful for detecting those at higher risk of experiencing or dying from CVD events.

Derivation and Validation of ICD-10 Codes for Identifying Incident Stroke

Claims data with International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes are routinely used in clinical research. However, the use of ICD-10 codes to define incident stroke has not been validated against expert-adjudicated outcomes in the US population. To develop and validate the accuracy of an ICD-10 code list to detect incident stroke events using Medicare inpatient fee-for-service claims data. This cohort study used data from 2 prospective population-based cohort studies, the Atherosclerosis Risk in Communities (ARIC) study and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, and included participants aged 65 years or older without prior stroke who had linked Medicare claims data. Stroke events in the ARIC and REGARDS studies were identified via active surveillance and adjudicated by expert review. Medicare-linked ARIC data (2016-2018) were used to develop a list of ICD-10 codes for incident stroke detection. The list was validated using Medicare-linked REGARDS data (2016-2019). Data were analyzed from September 1, 2022, through September 30, 2023. Stroke events detected in Medicare claims vs expert-adjudicated stroke events in the ARIC and REGARDS studies. The main outcomes were sensitivity and specificity of incident stroke detection using ICD-10 codes. In the ARIC study, there were 110 adjudicated incident stroke events among 5194 participants (mean [SD] age, 80.1 [5.3] years) over a median follow-up of 3.0 (range, 0.003-3.0) years. Most ARIC participants were women (3160 [60.8%]); 993 (19.1%) were Black and 4180 (80.5%) were White. Using the primary diagnosis code on a Medicare billing claim, the ICD-10 code list had a sensitivity of 81.8% (95% CI, 73.3%-88.5%) and a specificity of 99.1% (95% CI, 98.8%-99.3%) to detect incident stroke. Using any diagnosis code on a Medicare billing claim, the sensitivity was 94.5% (95% CI, 88.5%-98.0%) and the specificity was 98.4% (95% CI, 98.0%-98.8%). In the REGARDS study, there were 140 adjudicated incident strokes among 6359 participants (mean [SD] age, 75.8 [7.0] years) over a median follow-up of 4.0 (range, 0-4.0) years. More than half of the REGARDS participants were women (3351 [52.7%]); 1774 (27.9%) were Black and 4585 (72.1%) were White. For the primary diagnosis code, the ICD-10 code list had a sensitivity of 70.7% (95% CI, 63.2%-78.3%) and a specificity of 99.1% (95% CI, 98.9%-99.4%). For any diagnosis code, the ICD-10 code list had a sensitivity of 77.9% (95% CI, 71.0%-84.7%) and a specificity of 98.9% (95% CI, 98.6%-99.2%). These findings suggest that ICD-10 codes could be used to identify incident stroke events in Medicare claims with moderate sensitivity and high specificity.

Guilt by association: Plant-based foods can be incorporated into both healthy and unhealthy plant-based diet indices associated with coronary heart disease.

One approach to test for differential associations between plant foods with health uses a scoring approach: foods categorized into animal or 'healthy' plant-based or 'unhealthy' plant-based groups to construct a plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI). To evaluate robustness of associations between diet indices and incident coronary heart disease (CHD) risk when recategorizing food groups in indices. Using REasons for Geographic and Racial Differences in Stroke (REGARDS) data, we replicated a published use of the scoring approach. Using Cox proportional hazards regression, we assessed ramifications of the following on associations between diet indices and CHD risk: 1) reconfiguring foods within and among food groups, using potatoes as an example, 2) leave-one-out analysis for each of 12 plant-based food groups, and 3) agnostically redefining each food group as 'healthy' or 'unhealthy'. Over 153,286 person-years of follow-up, there were 868 cases of CHD. Replication analyses did not reach statistical significance. General patterns of magnitude of hazard ratios (HRs) in replication and reconfiguration models were PDI HRs < hPDI HRs < uPDI HRs for women, and hPDI < PDI < uPDI for men. Five models reconfiguring potatoes resulted in small, varied differences in PDI, hPDI, and uPDI associations. Leave-one-out analyses resulted in greater variation of associations between indices and CHD. In agnostic models, each plant-based food group was classified in indices as 'healthy' and 'unhealthy' with statistically significant beneficial or deleterious associations with CHD. Averaged over 4,096 models, HRs' shifts were small when food groups were moved between 'healthy' and 'unhealthy'. Statistically significant associations between hPDI, uPDI, and PDI and incident CHD were not replicated. Small perturbations of the scoring approach had varied impacts on HRs. Agnostically constructing diet indices demonstrated the potential for guilt (or benefit) by association: any of the food groups we studied could be categorized with others in an index showing beneficial or deleterious associations.

Variant level heritability estimates of type 2 diabetes in African Americans

Type 2 diabetes (T2D) is caused by both genetic and environmental factors and is associated with an increased risk of cardiorenal complications and mortality. Though disproportionately affected by the condition, African Americans (AA) are largely underrepresented in genetic studies of T2D, and few estimates of heritability have been calculated in this race group. Using genome-wide association study (GWAS) data paired with phenotypic data from ~ 19,300 AA participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, Genetics of Hypertension Associated Treatments (GenHAT) study, and the Electronic Medical Records and Genomics (eMERGE) network, we estimated narrow-sense heritability using two methods: Linkage-Disequilibrium Adjusted Kinships (LDAK) and Genome-Wide Complex Trait Analysis (GCTA). Study-level heritability estimates adjusting for age, sex, and genetic ancestry ranged from 18% to 34% across both methods. Overall, the current study narrows the expected range for T2D heritability in this race group compared to prior estimates, while providing new insight into the genetic basis of T2D in AAs for ongoing genetic discovery efforts.

Soluble CD14 and Incident Diabetes Risk: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

Soluble CD14 (sCD14) is an inflammation biomarker with higher concentrations in White than Black adults. Higher sCD14 is seen in insulin resistance and diabetes. There are limited data on the relationship between sCD14 and incident diabetes. To determine the association of sCD14 with incident diabetes risk in a large biracial US cohort and evaluate whether relationships differ by race. This study included 3401 Black and White participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study without baseline diabetes who completed baseline and follow-up in-home visits. Modified Poisson regression models estimated risk ratios (RR) of incident diabetes per 1-SD increment sCD14, with adjustment for risk factors. A sCD14-by-race interaction evaluated whether associations differed by race. There were 460 cases of incident diabetes over a mean 9.5 years of follow-up. The association of sCD14 with diabetes differed by race (P for interaction < .09). Stratifying by race, adjusting for age, sex, and region, higher sCD14 was associated with incident diabetes in White (RR: 1.15; 95% CI: 1.01, 1.33) but not Black participants (RR: 0.96; 95% CI: 0.86, 1.08). In models adjusted for clinical and sociodemographic diabetes risk factors, the association was attenuated among White participants (RR: 1.10; 95% CI: 0.95, 1.28) and remained null among Black participants (RR: 0.90; 95% CI: 0.80, 1.01). sCD14 was associated with incident diabetes risk in White but not Black adults, but this association was explained by diabetes risk factors.

Social Determinants of Health and Incident Apparent Treatment-Resistant Hypertension Among White and Black US Adults: The REGARDS Study.

We examined the association of multilevel social determinants of health with incident apparent treatment-resistant hypertension (aTRH). We analyzed data from 2774 White and 2257 Black US adults from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study taking antihypertensive medication without aTRH at baseline to estimate the association of social determinants of health with incident aTRH. Selection of social determinants of health was guided by the Healthy People 2030 domains of education, economic stability, social context, neighborhood environment, and health care access. Blood pressure (BP) was measured during study visits, and antihypertensive medication classes were identified through a pill bottle review. Incident aTRH was defined as (1) systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg, or systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg for those with diabetes or chronic kidney disease while taking ≥3 classes of antihypertensive medication or (2) taking ≥4 classes of antihypertensive medication regardless of BP level, at the follow-up visit. Over a median 9.5 years of follow-up, 15.9% of White and 24.0% of Black adults developed aTRH. A percent of the excess aTRH risk among Black versus White adults was mediated by low education (14.2%), low income (16.0%), not seeing a friend or relative in the past month (8.1%), not having someone to care for them if ill or disabled (7.6%), lack of health insurance (10.6%), living in a disadvantaged neighborhood (18.0%), and living in states with poor public health infrastructure (6.0%). Part of the association between race and incident aTRH risk was mediated by social determinants of health.

Life-space mobility and cognitive function: The REasons for geographic and racial differences in stroke (REGARDS) study.

Life-space mobility and cognitive function: The REasons for geographic and racial differences in stroke (REGARDS) study.

Development and validation of mortality prediction models based on the social determinants of health

BackgroundThere is no standardised approach to screening adults for social risk factors. The goal of this study was to develop mortality risk prediction models based on the social determinants of...

Sex-Associated Metabolites and Incident Stroke, Incident Coronary Heart Disease, Hypertension, and Chronic Kidney Disease in the REGARDS Cohort.

Sex disparities exist in cardiometabolic diseases. Metabolomic profiling offers insight into disease mechanisms, as the metabolome is influenced by environmental and genetic factors. We identified metabolites associated with sex and determined if sex-associated metabolites are associated with incident stoke, incident coronary heart disease, prevalent hypertension, and prevalent chronic kidney disease. Targeted metabolomics was conducted for 357 metabolites in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) case-cohort substudy for incident stroke. Weighted logistic regression models were used to identify metabolites associated with sex in REGARDS. Sex-associated metabolites were replicated in the HyperGEN (Hypertension Genetic Epidemiology Network) and using the literature. Weighted Cox proportional hazard models were used to evaluate associations between metabolites and incident stroke. Cox proportional hazard models were used to evaluate associations between metabolites and incident coronary heart disease. Weighted logistic regression models were used to evaluate associations between metabolites and hypertension and chronic kidney disease. Fifty-one replicated metabolites were associated with sex. Higher levels of 6 phosphatidylethanolamines were associated with incident stroke. No metabolites were associated with incident coronary heart disease. Higher levels of uric acid and leucine and lower levels of a lysophosphatidylcholine were associated with hypertension. Higher levels of indole-3-lactic acid, 7 phosphatidylethanolamines, and uric acid, and lower levels of betaine and bilirubin were associated with chronic kidney disease. These findings suggest that the sexual dimorphism of the metabolome may contribute to sex differences in stroke, hypertension, and chronic kidney disease.

Omega-3 Fatty Acids and Risk of Ischemic Stroke in REGARDS.

We examined associations between lipidomic profiles and incident ischemic stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Plasma lipids (n = 195) were measured from baseline blood samples, and lipids were consolidated into underlying factors using exploratory factor analysis. Cox proportional hazards models were used to test associations between lipid factors and incident stroke, linear regressions to determine associations between dietary intake and lipid factors, and the inverse odds ratio weighting (IORW) approach to test mediation. The study followed participants over a median (IQR) of 7 (3.4-11) years, and the case-cohort substudy included 1075 incident ischemic stroke and 968 non-stroke participants. One lipid factor, enriched for docosahexaenoic acid (DHA, an omega-3 fatty acid), was inversely associated with stroke risk in a base model (HR = 0.84; 95%CI 0.79-0.90; P = 8.33 × 10-8) and fully adjusted model (HR = 0.88; 95%CI 0.83-0.94; P = 2.79 × 10-4). This factor was associated with a healthy diet pattern (β = 0.21; 95%CI 0.12-0.30; P = 2.06 × 10-6), specifically with fish intake (β = 1.96; 95%CI 0.95-2.96; P = 1.36 × 10-4). DHA was a mediator between fish intake and incident ischemic stroke (30% P = 5.78 × 10-3). Taken together, DHA-containing plasma lipids were inversely associated with incident ischemic stroke and mediated the relationship between fish intake and stroke risk.