Plasma Metabolites and Life's Simple 7 in REGARDS.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (ß, -0.46 [95% CI, -0.65 to -0.27]; P=2.87×10-6), cotinine (ß, -0.49 [95% CI, -0.70 to -0.28]; P=7.74×10-6), and acetylneuraminic acid (ß, -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. CONCLUSIONS: We identified guanosine, cotinine, and acetylneuraminic acid that were associated with LS7, incident ischemic stroke, and mediated the relationship between LS7 and ischemic stroke.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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]). CONCLUSIONS: 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.

Path-specific causal decomposition analysis with multiple correlated mediator variables.

A causal decomposition analysis allows researchers to determine whether the difference in a health outcome between two groups can be attributed to a difference in each group's distribution of one or more modifiable mediator variables. With this knowledge, researchers and policymakers can focus on designing interventions that target these mediator variables. Existing methods for causal decomposition analysis either focus on one mediator variable or assume that each mediator variable is conditionally independent given the group label and the mediator-outcome confounders. In this article, we propose a flexible causal decomposition analysis method that can accommodate multiple correlated and interacting mediator variables, which are frequently seen in studies of health behaviors and studies of environmental pollutants. We extend a Monte Carlo-based causal decomposition analysis method to this setting by using a multivariate mediator model that can accommodate any combination of binary and continuous mediator variables. Furthermore, we state the causal assumptions needed to identify both joint and path-specific decomposition effects through each mediator variable. To illustrate the reduction in bias and confidence interval width of the decomposition effects under our proposed method, we perform a simulation study. We also apply our approach to examine whether differences in smoking status and dietary inflammation score explain any of the Black-White differences in incident diabetes using data from a national cohort study.

Population-average mediation analysis for zero-inflated count outcomes.

Mediation analysis is an increasingly popular statistical method for explaining causal pathways to inform intervention. While methods have increased, there is still a dearth of robust mediation methods for count outcomes with excess zeroes. Current mediation methods addressing this issue are computationally intensive, biased, or challenging to interpret. To overcome these limitations, we propose a new mediation methodology for zero-inflated count outcomes using the marginalized zero-inflated Poisson (MZIP) model and the counterfactual approach to mediation. This novel work gives population-average mediation effects whose variance can be estimated rapidly via delta method. This methodology is extended to cases with exposure-mediator interactions. We apply this novel methodology to explore if diabetes diagnosis can explain BMI differences in healthcare utilization and test model performance via simulations comparing the proposed MZIP method to existing zero-inflated and Poisson methods. We find that our proposed method minimizes bias and computation time compared to alternative approaches while allowing for straight-forward interpretations.

Plasma proenkephalin A and incident chronic kidney disease and albuminuria in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.

BACKGROUND: Plasma proenkephalin A (PENK-A) is a precursor of active enkephalins. Higher blood concentrations have been associated with estimated glomerular filtration rate (eGFR) decline in European populations. Due to the significant disparity in incident chronic kidney disease (CKD) between White and Black people, we evaluated the association of PENK-A with incident CKD and other kidney outcomes among a biracial cohort in the U.S. METHODS: In a nested cohort of 4,400 participants among the REasons for Geographic And Racial Differences in Stroke, we determined the association between baseline PENK-A concentration and incident CKD using the creatinine-cystatin C CKD-EPI 2021 equation without race coefficient, significant eGFR decline, and incident albuminuria between baseline and a follow-up visit 9.4 years later. We tested for race and sex interactions. We used inverse probability sampling weights to account for the sampling design. RESULTS: At baseline, mean (SD) age was 64 (8) years, 49% were women, and 52% were Black participants. 8.5% developed CKD, 21% experienced ≥ 30% decline in eGFR and 18% developed albuminuria. There was no association between PENK-A and incident CKD and no difference by race or sex. However, higher PENK-A was associated with increased odds of progressive eGFR decline (OR: 1.12; 95% CI 1.00, 1.25). Higher PENK-A concentration was strongly associated with incident albuminuria among patients without diabetes mellitus (OR: 1.29; 95% CI 1.09, 1.53). CONCLUSION: While PENK-A was not associated with incident CKD, its associations with progression of CKD and incident albuminuria, among patients without diabetes, suggest that it might be a useful tool in the evaluation of kidney disease among White and Black patients.

Regional and rural-urban patterns in the prevalence of diagnosed hypertension among older U.S. adults with diabetes, 2005-2017.

BACKGROUND: Hypertension prevalence among the overall US adult population has been relatively stable during the last two decades. However, whether this stabilization has occurred across rural-urban communities and across different geographic regions is unknown, particularly among older adults with diabetes who are likely to have concomitant cardiovascular risk factors. METHODS: This serial cross-sectional analysis used the 5% national sample of Medicare administrative claims data (n = 3,516,541) to examine temporal trends (2005-2017) in diagnosed hypertension among older adults with diabetes, across urban-rural communities and US census regions (Northeast, Midwest, South, and West). Joinpoint regression was used to obtain annual percent change (APC) in hypertension prevalence across rural-urban communities and geographic regions, and multivariable adjusted regression was used to assess associations between rural-urban communities and hypertension prevalence. RESULTS: The APC in the prevalence of hypertension was higher during 2005-2010, and there was a slowdown in the increase during 2011-2017 across all regions, with significant variations across rural-urban communities within each of the regions. In the regression analysis, in the adjusted model, older adults living in non-core (most rural) areas in the Midwest (PR = 0.988, 95% CI: 0.981-0.995) and West (PR = 0.935, 95% CI: 0.923-0.946) had lower hypertension prevalence than their regional counterparts living in large central metro areas. CONCLUSIONS: Although the magnitudes of these associations are small, differences in hypertension prevalence across rural-urban areas and geographic regions may have implications for targeted interventions to improve chronic disease prevention and management.

N-Terminal Pro-B-Type Natriuretic Peptide and Risk for Diabetes Mellitus and Metabolic Syndrome.

CONTEXT: Natriuretic peptide concentrations are inversely associated with risk of diabetes mellitus and may be protective from metabolic dysfunction. OBJECTIVE: We studied associations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with incident diabetes, metabolic syndrome (MetS), and MetS components. DESIGN/SETTING/PARTICIPANTS: 2,899 participants with baseline (2003-2007) and follow-up (2013-2016) examinations and baseline NT-proBNP measurement in the REasons for Geographic And Racial Differences in Stroke study. Logistic regression models were fitted to incident MetS, MetS components, and diabetes; covariates included demographics, risk and laboratory factors. MAIN OUTCOME MEASURES: Incident diabetes, defined as fasting glucose ≥126 mg/dL, random glucose ≥200 mg/dL, or use of insulin or hypoglycemic drugs at follow-up but not baseline. Incident MetS, in participants with ≥3 harmonized criteria at follow-up and <3 at baseline. RESULTS: 310 participants (2,364 at risk) developed diabetes and 361 (2,059 at risk) developed MetS over mean 9.4 years follow-up. NT-proBNP was inversely associated with odds of incident diabetes (fully-adjusted OR per-SD higher log NT-proBNP 0.80, 95% CI 0.69-0.93) and MetS in the highest vs. lowest quartile only (fully-adjusted OR 0.59, 95% CI 0.37-0.92); the linear association with incident MetS was not statistically significant. NT-proBNP was inversely associated with incident dysglycemia in all models (fully-adjusted OR per-SD log NT-proBNP 0.65, 95% CI 0.53-0.79), but not with other MetS components. Effect modification by sex, race, age, or BMI was not observed. CONCLUSIONS: NT-proBNP was inversely associated with odds of diabetes, MetS, and the MetS dysglycemia component. The metabolic implications of B-type natriuretic peptides appear important for glycemic homeostasis.

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

Context: 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. Objective: To determine the association of sCD14 with incident diabetes risk in a large biracial US cohort and evaluate whether relationships differ by race. Design: 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. Results: 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). Conclusion: sCD14 was associated with incident diabetes risk in White but not Black adults, but this association was explained by diabetes risk factors.

Application of marginalized zero-inflated models when mediators have excess zeroes.

Mediation analysis has become increasingly popular over the last decade as researchers are interested in assessing mechanistic pathways for intervention. Although available methods have increased, there are still limited options for mediation analysis with zero-inflated count variables where the distribution of response has a "cluster" of data at the zero value (i.e. distribution of number of cigarettes smoked per day, where nonsmokers cluster at zero cigarettes). The currently available methods do not obtain unbiased population average effects of mediation effects. In this paper, we propose an extension of the counterfactual approach to mediation with direct and indirect effects to scenarios where the mediator is a count variable with excess zeroes by utilizing the Marginalized Zero-Inflated Poisson Model (MZIP) for the mediator model. We derive direct and indirect effects for continuous, binary, and count outcomes, as well as adapt to allow mediator-exposure interactions. Our proposed work allows straightforward calculation of direct and indirect effects for the overall population mean values of the mediator, for scenarios in which researchers are interested in generalizing direct and indirect effects to the population. We apply this novel methodology to an application observing how alcohol consumption may explain sex differences in cholesterol and assess model performance via a simulation study comparing the proposed MZIP mediator framework to existing methods for marginal mediator effects.

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

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Endothelial Dysfunction Biomarkers and CKD Incidence in the REGARDS Cohort.

Introduction: Chronic kidney disease (CKD) is only partly caused by traditional risk factors. Endothelial dysfunction is common in CKD and may contribute to CKD incidence. We studied the association of circulating biomarkers reflecting endothelial dysfunction with incident CKD. Methods: The Reasons for Geographical and Racial Differences in Stroke (REGARDS) study is a prospective cohort of 30,239 Black or White adults aged ≥45 years. Baseline levels of intercellular cellular adhesion molecule 1 (ICAM-1), vascular cellular adhesion molecule 1 (VCAM-1), factor VIII (FVIII), and E-selectin were measured in 3300 participants without baseline CKD or albuminuria who attended a second visit 9.4 years later. Kidney outcomes were incident CKD (estimated glomerular filtration rate [eGFR] <60 ml/min per 1.73 m2 and ≥40% decline or onset of new end-stage kidney disease), incident ≥30% eGFR decline, and incident albuminuria (albumin-to-creatinine ratio [ACR] ≥30 mg/g). Sequentially adjusted logistic regression models assessed the association of biomarkers with kidney outcomes. Results: Median age of participants was 62 years, 49% were women, and 46% identified as Black. Of the participants, 228 (6.9%) developed CKD, 613 (18.9%) experienced ≥30% decline in eGFR, and 356 (11.4%) developed albuminuria. The adjusted odds ratios (ORs) for incident CKD per 1 SD increment biomarker was 1.12 for ICAM-1 (95% confidence interval [CI]: 1.02-1.22), 1.10 for VCAM-1 (95% CI: 1.01-1.20), 1.15 for FVIII (95% CI: 1.06-1.24), and 1.10 for E-selectin (95% CI: 1.01-1.20). Results were similar for incident ≥30% eGFR decline but not albuminuria, where only higher FVIII was positively associated. Conclusion: Higher concentration of ICAM-1, VCAM-1, FVIII, and E-selectin were associated with incident CKD and ≥30% eGFR decline in a large cohort study. Higher FVIII was also associated with incident albuminuria.

Interleukin-6, Diabetes, and Metabolic Syndrome in a Biracial Cohort: The Reasons for Geographic and Racial Differences in Stroke Cohort.

OBJECTIVE: Black Americans have a greater risk of type 2 diabetes than White Americans. The proinflammatory cytokine interleukin-6 (IL-6) is implicated in diabetes pathogenesis, and IL-6 levels are higher in Black individuals. This study investigated associations of IL-6 with incident diabetes and metabolic syndrome in a biracial cohort. RESEARCH DESIGN AND METHODS: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study enrolled 30,239 Black and White adults age ≥45 years in 2003-2007, with a follow-up ∼9.5 years later. Baseline plasma IL-6 was measured in 3,399 participants at risk of incident diabetes and 1,871 at risk of metabolic syndrome. Relative risk (RR) by IL-6 was estimated with modified Poisson regression for both groups. RESULTS: Incident diabetes occurred in 14% and metabolic syndrome in 20%; both rates rose across IL-6 quartiles. There was a three-way interaction of IL-6, race, and central adiposity for incident diabetes (P = 8 × 10-5). In Black participants with and without central adiposity, RRs were 2.02 (95% CI 1.00-4.07) and 1.66 (1.00-2.75) for the fourth compared with first IL-6 quartile, respectively. The corresponding RRs were 1.73 (0.92-3.26) and 2.34 (1.17-4.66) in White participants. The pattern was similar for IL-6 and metabolic syndrome. CONCLUSIONS: Although IL-6 was higher in Black than in White participants and those with central adiposity, the association of IL-6 with diabetes risk was statistically significant only among White participants without central adiposity. The association with metabolic syndrome risk was similarly stronger in low-risk groups. The results support the concept of interventions to lower inflammation in diabetes prevention, but to reduce race disparities, better biomarkers are needed.

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 (ß = 0.21; 95%CI 0.12-0.30; P = 2.06 × 10-6), specifically with fish intake (ß = 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.

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

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.

Race-specific associations: inflammatory mediators and chronic low back pain.

ABSTRACT: Chronic low back pain (cLBP) is a global health crisis that disproportionately burdens non-Hispanic Black (NHB) individuals, compared with those who identify as non-Hispanic White (NHW). Despite the growing personal and societal impact of cLBP, its biological underpinnings remain poorly understood. To elucidate the biological factors that underlie the racial disparities in cLBP, this study sought to determine whether inflammatory mediators associated with pain interference (PI), pain at rest (PAR), and movement-evoked pain (MEP) differ as a function of racial identity. Blood samples were collected from 156 individuals with cLBP (n = 98 NHB participants, n = 58 NHW participants). Enzyme-linked immunosorbent assay and multiplex assays were used to quantify concentrations of proinflammatory (fibrinogen, C-reactive protein [CRP], serum amyloid A, tumor necrosis factor α [TNF-α], and interleukin [IL]-1α, IL-1ß, and IL-6) and anti-inflammatory markers (IL-4 and IL-13). Spearman rho correlations were used to assess associations among markers of inflammation and PI, PAR, and MEP using the Brief Pain Inventory-Short Form. Analyses revealed that for NHW patients, CRP, serum amyloid A, and IL-6 were positively associated with cLBP outcomes and IL-4 was inversely associated with PAR and MEP. However, for NHB patients, only IL-1α was positively associated with PAR. Our findings suggest that, while there are associations between inflammation and cLBP outcomes, the biomarkers that underlie the inflammation could very well differ as a function of racialized minority group. However, more research with racially inclusive samples is needed to elucidate the mechanisms that may contribute to racial disparities in cLBP.

Cytokines, C-Reactive Protein, and Risk of Incident Hypertension in the REGARDS Study.

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)-1ß, 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-1ß 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-1ß, 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.

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

BACKGROUND: 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. METHODS AND RESULTS: 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). CONCLUSIONS: These findings emphasize the importance of caregiver feedback in predicting cognitive consequences of stroke.