Development and validation of a risk model for hospital-acquired venous thrombosis: the Medical Inpatients Thrombosis and Hemostasis study.

BACKGROUND: Regulatory organizations recommend assessing hospital-acquired (HA) venous thromboembolism (VTE) risk for medical inpatients. OBJECTIVES: To develop and validate a risk assessment model (RAM) for HA-VTE in medical inpatients using objective and assessable risk factors knowable at admission. METHODS: The development cohort included people admitted to medical services at the University of Vermont Medical Center (Burlington, Vermont) between 2010 and 2019, and the validation cohorts included people admitted to Hennepin County Medical Center (Minneapolis, Minnesota), University of Michigan Medical Center (Ann Arbor, Michigan), and Harris Health Systems (Houston, Texas). Individuals with VTE at admission, aged <18 years, and admitted for <1 midnight were excluded. We used a Bayesian penalized regression technique to select candidate HA-VTE risk factors for final inclusion in the RAM. RESULTS: The development cohort included 60 633 admissions and 227 HA-VTE, and the validation cohorts included 111 269 admissions and 651 HA-VTE. Seven HA-VTE risk factors with t statistics ≥1.5 were included in the RAM: history of VTE, low hemoglobin level, elevated creatinine level, active cancer, hyponatremia, increased red cell distribution width, and malnutrition. The areas under the receiver operating characteristic curve and calibration slope were 0.72 and 1.10, respectively. The areas under the receiver operating characteristic curve and calibration slope were 0.70 and 0.93 at Hennepin County Medical Center, 0.70 and 0.87 at the University of Michigan Medical Center, and 0.71 and 1.00 at Harris Health Systems, respectively. The RAM performed well stratified by age, sex, and race. CONCLUSION: We developed and validated a RAM for HA-VTE in medical inpatients. By quantifying risk, clinicians can determine the potential benefits of measures to reduce HA-VTE.

Rural versus Urban Residence in Adulthood and Incident Cognitive Impairment.

INTRODUCTION: Rural versus urban living is a social determinant of cognitive health. We estimated the association of rural versus urban residence in the USA with incident cognitive impairment (ICI) and assessed effect heterogeneity by sociodemographic, behavioral, and clinical factors. METHODS: The Reasons for Geographic and Racial Differences in Stroke Study (REGARDS) is a population-based prospective observational cohort of 30,239 adults, 57% female, 36% Black, aged 45+ years, sampled from 48 contiguous states in the USA in 2003-2007. We analyzed 20,878 participants who at baseline were cognitively intact with no history of stroke and had ICI assessed on average 9.4 years later. We classified participants' home addresses at baseline as urban (population ≥50,000), large rural (10,000-49,999), or small rural (≤9,999) by Rural-Urban Commuting Area codes. We defined ICI as ≥1.5 SD below the mean on at least 2 of the following tests: word list learning, word list delayed recall, and animal naming. RESULTS: Participants' home addresses were 79.8% urban, 11.7% large rural, and 8.5% small rural. ICI occurred in 1,658 participants (7.9%). Small rural residents had higher odds of ICI than urban residents, adjusted for age, sex, race, region, and education (OR = 1.34 [95% CI: 1.10, 1.64]), and after further adjustment for income, health behaviors, and clinical characteristics (OR = 1.24 [95% CI: 1.02, 1.53]). Former smoking versus never, nondrinking versus light alcohol drinking, no exercise versus ≥4 times/week, CES-D depressive symptom score of 2 versus 0, and fair versus excellent self-rated health had stronger associations with ICI in small rural areas than in urban areas. For example, in urban areas, lack of exercise was not associated with ICI (OR = 0.90 [95% CI: 0.77, 1.06]); however, lack of exercise combined with small rural residence was associated with 1.45 times the odds of ICI compared with ≥4 bouts of exercise/week in urban areas (95% CI: 1.03, 2.03). Overall, large rural residence was not associated with ICI; however, black race, hypertension, and depressive symptoms had somewhat weaker associations with ICI, and heavy alcohol drinking a stronger association with ICI, in large rural areas than in urban areas. CONCLUSION: Small rural residence was associated with ICI among USA adults. Further research to better understand why rural residents are at higher risk for developing ICI and mechanisms to ameliorate that risk will support efforts to advance rural public health.

The associations between prenatal phthalate exposure measured in child meconium and cognitive functioning of 12-month-old children in two cohorts at elevated risk for adverse neurodevelopment.

BACKGROUND: Phthalate metabolites in gestational-maternal urine represents short-term maternal exposure, but meconium, the newborn's first stool may better capture cumulative fetal exposure. We quantified phthalate metabolites in meconium from two cohorts of children at higher risk of adverse neurodevelopment and evaluated associations with their cognitive function at 12 months. METHODS: Meconium phthalate metabolites were quantified in the Safe Passage Study (SPS), N = 720, a pregnancy cohort with high community-levels of prenatal alcohol use, and the Early Autism Risk Longitudinal Investigation (EARLI), N = 236, a high familial autism risk pregnancy cohort. EARLI also had second and third trimester (T2/T3) maternal urine for exposure assessment. Molar sum of di (2-ethylhexyl) (∑DEHP) metabolites and an anti-androgenic score (AAS) using mono-isobutyl, mono-n-butyl, monobenzyl (MBZP), and DEHP metabolites were computed. Cognitive function was assessed at 12 months using the Mullen Scales of Early Learning-Composite (ELC). Multivariable linear regression assessed associations between loge-transformed metabolites and ELC. Quadratic terms explored nonlinearity and interaction terms of metabolite by child's sex examined effect modification. RESULTS: In SPS, MBzP (ßLinear = -6.73; 95% CI: 12.04, -1.42; ßquadratic = 1.95; 0.27, 3.62) and mono (2-ethyl-5-carboxypentyl), (ßLinear = -3.81; -7.53, -0.27; ßquadratic = 0.93; 0.09, 1.77) had U-shaped associations with ELC. In EARLI, T2 urine mono-carboxyisononyl was associated with linear decrease in ELC, indicating lower cognitive function. Interaction with sex was suggested (P < 0.2) for several urine metabolites, mostly indicating negative association between phthalates and ELC among girls but reversed among boys. Only mono-isononyl phthalate and ∑DEHP had consistent main effect associations across matrixes and cohorts, but similar interaction with sex was observed for meconium-measured ∑DEHP, AAS, MBzP, and mono (2-ethylhexyl) in both cohorts. CONCLUSIONS: Few phthalate metabolites were consistently associated with children's cognitive function, but a similar set of meconium metabolites from both cohorts displayed sex-specific associations. Gestational phthalate exposure may have sexually-dimorphic associations with early cognitive function in children at higher risk for adverse neurodevelopment.

Connecting the Dots: a cluster-randomized clinical trial integrating standardized autism spectrum disorders screening, high-quality treatment, and long-term outcomes.

BACKGROUND: Autism spectrum disorder (ASD) affects one in 54 children in the United States of America, and supporting people with ASD across the lifespan presents challenges that impact individuals, families, and communities and can be quite costly. The American Academy of Pediatrics has issued recommendations for routine ASD screening at 18 and 24 months, but some research suggests that few pediatricians perform high-fidelity, standardized screening universally. Furthermore, the United States Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against universal ASD screening. The objective of this study is to test the hypothesis that children with ASD who have high fidelity; standardized screening will achieve superior outcomes at 5 years of age compared to children receiving usual care ASD detection strategies. METHODS: This is a cluster-randomized, controlled clinical trial in 3 sites in the USA. Pediatric practices will be randomized to implement universal, standardized, high-fidelity toddler screening or usual care, with randomization stratified by the practice size. The study will enroll 3450 children, approximately half in each group. From this sample, we anticipate 100 children to be diagnosed with ASD. Children in both groups receiving an ASD diagnosis will be administered the Early Start Denver Model, an evidence-based early intervention addressing social, communication, and cognitive functioning. Treatment will last for 1 year, with up to 20 h per week of therapy for children with ASD. RESULTS: Primary outcomes measured at baseline, following treatment, and at 4 and 5 years of age include ASD symptom severity (Brief Observation of Social Communication Change (BOSCC)) and cognitive functioning (Mullen Scales of Early Learning (MSEL) and Differential Abilities Scale-II (DAS-II)). Secondary outcomes in children include measures of adaptive functioning, ASD symptoms, and kindergarten readiness; secondary analyses will also examine stress and empowerment among parents. Several novel exploratory measures will be included as well. The study will utilize a modified intention-to-treat analysis. CONCLUSIONS: This trial will evaluate the impact of universal, standardized, high-fidelity screening for ASD among children at 18 months of age, with a goal of providing evidence to support this strategy to detect ASD in toddlers in order to start treatment as young as possible and maximize outcomes. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board at Drexel University (IRB protocol: 1607004653). All findings will be provided by the principal investigator via email; data will be available through the NIMH Data Archive ( https://nda.nih.gov/ ). TRIAL REGISTRATION: ClinicalTrials.gov NCT03333629 . Registered on November 7, 2017.

Determinants of cigarette smoking status in a national cohort of black and white adult ever smokers in the USA: a cross-sectional analysis of the REGARDS study.

OBJECTIVES: While awareness of cigarette smoking's harmful effects has increased, determinants associated with smoking status remain understudied, including potential racial differences. We aim to examine factors associated with former versus current smoking status and assess whether these associations differed by race. SETTING: We performed a cross-sectional analysis using the population-based Reasons for Geographic and Racial Differences in Stroke(REGARDS)study. OUTCOME MEASURES: Logistic regression was used to calculate the OR of former smoking status compared with current smoking status with risk factors of interest. Race interactions were tested using multiplicative interaction terms. RESULTS: 16 463 participants reported smoking at least 100 cigarettes in their lifetime. Seventy-three per cent (n=12 067) self-reported former-smoker status. Physical activity (reference (REF) <3×/week; >3×/week: OR=1.26, 95% CI 1.11 to 1.43), adherence to Mediterranean diet (REF: low; medium: OR=1.46, 95% CI 1.27 to 1.67; high: OR=2.20, 95% CI 1.84 to 2.64), daily television viewing time (REF: >4 hours; <1 hour: OR=1.32, 95% CI 1.10 to 1.60) and abstinence from alcohol use (REF: heavy; none: OR=1.50, 95% CI 1.18 to 1.91) were associated with former-smoker status. Male sex, higher education and income $35 000-$74 000 (REF: <$20 000) were also associated with former-smoker status. Factors associated with lower odds of reporting former-smoker status were younger age (REF: ≥65 years; 45-64 years: OR=0.34, 95% CI 0.29 to 0.39), black race (OR=0.62, 95% CI 0.53 to 0.72) and single marital status (REF: married status; OR=0.66, 95% CI 0.51 to 0.87), being divorced (OR=0.60, 95% CI 0.50 to 0.72) or widowed (OR=0.70, 95% CI 0.57 to 0.85). Significant interactions were observed between race and alcohol use and dyslipidaemia, such that black participants had higher odds of reporting former-smoker status if they were abstinent from alcohol (OR=2.32, 95% CI 1.47 to 3.68) or had a history of dyslipidaemia (OR=1.31, 95% CI 1.06 to 1.62), whereas these relationships were not statistically significant in white participants. CONCLUSION: Efforts to promote tobacco cessation should consist of targeted behavioural interventions that incorporate racial differences.

Inflammatory cytokines and ischemic stroke risk: The REGARDS cohort.

OBJECTIVE: We studied circulating interleukin (IL)-6, IL-8, and IL-10 concentrations and incident ischemic stroke risk in a biracial cohort, and determined if these cytokines mediated the racial disparity in stroke incidence affecting the black population. METHODS: The Reasons for Geographic and Racial Differences in Stroke study enrolled 30,237 black and white men and women age ≥45 in 2003-2007. We measured baseline IL-6, IL-8, and IL-10 in a case-cohort study of 557 participants with incident stroke over 5.4 years and 951 participants in a cohort sample. RESULTS: IL-6, but not IL-8 or IL-10, was higher in cases compared to the cohort sample (mean 4.5 vs 3.7 ng/mL; p < 0.001). Only IL-6 was associated with stroke risk factors. Adjusting for age, sex, and race, the hazard ratio (HR; 95% confidence interval) for incident stroke for the highest vs lowest quartile of IL-6 was 2.4 (1.6-3.4). HRs for the highest vs lowest quartiles of IL-8 and IL-10 were 1.5 (1.0-2.1) and 1.4 (1.0-1.9), respectively. After additional adjustment for stroke risk factors, only higher IL-6 remained associated with stroke risk (HR 2.0; 1.2-3.1). Associations did not differ by race. Mediation analyses showed that IL-6 mediated the black-white disparity in stroke risk, but mediation was via IL-6 associations with stroke risk factors. CONCLUSIONS: In this biracial population-based sample, IL-6 was strongly associated with risk of incident stroke and mediated the racial disparity in stroke via inflammatory effects of risk factors. Further study on the clinical utility of IL-6 measurement in stroke risk assessment would be helpful.

Association of secondhand tobacco smoke exposure during childhood on adult cardiovascular disease risk among never-smokers.

PURPOSE: Adult secondhand tobacco smoke (SHS) exposure is related to stroke and coronary heart disease (CHD) risk, but long-term effects are less clear. We evaluated whether childhood SHS exposure affects subsequent stroke or CHD risk among adult black and white never-smokers followed for stroke and CHD. METHODS: In this prospective cohort study, inverse probability weights were calculated to correct for bias due to attrition and survey nonresponse. Cox proportional hazards models were used to assess hazard ratios and 95% confidence intervals for stroke or CHD, separately, by number of childhood household smokers. RESULTS: Of 13,142 eligible participants, 6136 had childhood SHS exposure assessed. Baseline mean (SD) age was 63.5 (9.0), 65% were female, 30% black, 46% reported 0 childhood household smokers, 36% reported 1, and 18% reported 2+. In 60,649 person-years, 174 strokes were observed (2.9% of participants), and in 45,195 person-years, 114 CHD events were observed (2.1% of participants). The weighted and adjusted hazard ratios (95% confidence intervals) of stroke for 2+ versus 0 childhood household smokers was 1.66 (1.29-2.13) and was 1.15 (0.82-1.59) for CHD. CONCLUSIONS: We observed a significant association between childhood SHS exposure and stroke, but not CHD, after age 45 years and adjusting for missing information.

Urinary cadmium concentration and the risk of ischemic stroke.

OBJECTIVES: To examine the association between urinary cadmium levels and the incidence of ischemic stroke and to explore possible effect modifications. METHODS: A case-cohort study was designed nested in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, including 680 adjudicated incident cases of ischemic stroke and 2,540 participants in a randomly selected subcohort. Urinary creatinine-corrected cadmium concentration was measured at baseline. Multivariable-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated with the Barlow weighting method for the Cox proportional hazards regression model. RESULTS: The median urinary cadmium concentration was 0.42 (interquartile range 0.27-0.68) µg/g creatinine. After adjustment for potential confounders, urinary cadmium was associated with increased incidence of ischemic stroke (quintile 5 vs quintile 1: HR 1.50, 95% CI 1.01-2.22, p for trend = 0.02). The observed association was more pronounced among participants in the lowest serum zinc tertile (tertile 3 vs tertile 1: HR 1.82, 95% CI 1.06-3.11, p for trend = 0.004, p for interaction = 0.05) but was attenuated and became nonsignificant among never smokers (tertile 3 vs tertile 1: never smokers: HR 1.27, 95% CI 0.80-2.03, p for trend = 0.29; ever smokers: HR 1.60, 95% CI 1.06-2.43, p for trend = 0.07, p for interaction = 0.51). CONCLUSIONS: Findings from this study suggest that cadmium exposure may be an independent risk factor for ischemic stroke in the US general population. Never smoking and maintaining a high serum zinc level may ameliorate the potential adverse effects of cadmium exposure.

Fine Particulate Matter Pollution and Risk of Community-Acquired Sepsis.

While air pollution has been associated with health complications, its effect on sepsis risk is unknown. We examined the association between fine particulate matter (PM2.5) air pollution and risk of sepsis hospitalization. We analyzed data from the 30,239 community-dwelling adults in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort linked with satellite-derived measures of PM2.5 data. We defined sepsis as a hospital admission for a serious infection with ≥2 systemic inflammatory response (SIRS) criteria. We performed incidence density sampling to match sepsis cases with 4 controls by age (±5 years), sex, and race. For each matched group we calculated mean daily PM2.5 exposures for short-term (30-day) and long-term (one-year) periods preceding the sepsis event. We used conditional logistic regression to evaluate the association between PM2.5 exposure and sepsis, adjusting for education, income, region, temperature, urbanicity, tobacco and alcohol use, and medical conditions. We matched 1386 sepsis cases with 5544 non-sepsis controls. Mean 30-day PM2.5 exposure levels (Cases 12.44 vs. Controls 12.34 µg/m³; p = 0.28) and mean one-year PM2.5 exposure levels (Cases 12.53 vs. Controls 12.50 µg/m³; p = 0.66) were similar between cases and controls. In adjusted models, there were no associations between 30-day PM2.5 exposure levels and sepsis (4th vs. 1st quartiles OR: 1.06, 95% CI: 0.85⁻1.32). Similarly, there were no associations between one-year PM2.5 exposure levels and sepsis risk (4th vs. 1st quartiles OR: 0.96, 95% CI: 0.78⁻1.18). In the REGARDS cohort, PM2.5 air pollution exposure was not associated with risk of sepsis.

Analyses of genome wide association data, cytokines, and gene expression in African-Americans with benign ethnic neutropenia.

BACKGROUND: Benign ethnic neutropenia (BEN) is a hematologic condition associated with people of African ancestry and specific Middle Eastern ethnic groups. Prior genetic association studies in large population showed that rs2814778 in Duffy Antigen Receptor for Chemokines (DARC) gene, specifically DARC null red cell phenotype, was associated with BEN. However, the mechanism of this red cell phenotype leading to low white cell count remained elusive. METHODS: We conducted an extreme phenotype design genome-wide association study (GWAS), analyzed ~16 million single nucleotide polymorphisms (SNP) in 1,178 African-Americans individuals from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study and replicated from 819 African-American participants in the Atherosclerosis Risk in Communities (ARIC) study. Conditional analyses on rs2814778 were performed to identify additional association signals on chromosome 1q22. In a separate cohort of healthy individuals with and without BEN, whole genome gene expression from peripheral blood neutrophils were analyzed for DARC. RESULTS: We confirmed that rs2814778 in DARC was associated with BEN (p = 4.09×10-53). Conditioning on rs2814778 abolished other significant chromosome 1 associations. Inflammatory cytokines (IL-2, 6, and 10) in participants in the Howard University Family Study (HUFS) and Multi-Ethnic Study in Atherosclerosis (MESA) showed similar levels in individuals homozygous for the rs2814778 allele compared to others, indicating cytokine sink hypothesis played a minor role in leukocyte homeostasis. Gene expression in neutrophils of individuals with and without BEN was also similar except for low DARC expression in BEN, suggesting normal function. BEN neutrophils had slightly activated profiles in leukocyte migration and hematopoietic stem cell mobilization pathways (expression fold change <2). CONCLUSIONS: These results in humans support the notion of DARC null erythroid progenitors preferentially differentiating to myeloid cells, leading to activated DARC null neutrophils egressing from circulation to the spleen, and causing relative neutropenia. Collectively, these human data sufficiently explained the mechanism DARC null red cell phenotype causing BEN and further provided a biologic basis that BEN is clinically benign.

Smoking and risk of atrial fibrillation in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

BACKGROUND: Whether smoking increases the risk of atrial fibrillation (AF) remains debatable due to inconsistent reports. METHODS: We examined the association between smoking and incident AF in 11,047 participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, one of the largest biracial, population-based cohort studies in the USA. Baseline (2003-2007) cigarette smoking status and amount (pack-years) were self-reported. Incident AF was determined by electrocardiography and history of a prior physician diagnosis at a follow-up examination conducted after a median of 10.6 years. RESULTS: During follow-up, 954 incident AF cases were identified; 9.5% in smokers vs. 7.8% in non-smokers; p<0.001. In a model adjusted for socio-demographics, smoking (ever vs. never) was associated with a 15% increased risk of AF [OR (95%CI): 1.15(1.00, 1.31)], but this association was no longer significant after further adjustment for cardiovascular risk factors [OR (95% CI): 1.12 (0.97, 1.29)]. However, heterogeneities in the association were observed among subgroups; the association was stronger in young vs. old participants [OR (95%CI): 1.31 (1.03, 1.67) vs. 0.99 (0.83-1.18) respectively; interaction p-value=0.005] and in those with vs. without prior cardiovascular disease [OR (95%CI): 1.18 (0.90, 1.56) vs. 1.06 (0.90, 1.25) respectively; interaction p-value 0.0307]. Also, the association was significant in blacks but not in whites [OR (95%CI): 1.51 (1.12, 2.05) vs. 0.99 (0.84, 1.16), respectively], but the interaction p-value did not reach statistical significance (interaction p-value=0.65). CONCLUSIONS: The association between smoking and AF is possibly mediated by a higher prevalence of cardiovascular risk factors in smokers, but there is marked heterogeneity in the strength of this association among subgroups which may explain the conflicting results in prior studies.

Heat Maps of Hypertension, Diabetes Mellitus, and Smoking in the Continental United States.

BACKGROUND: Geographic variations in cardiovascular mortality are substantial, but descriptions of geographic variations in major cardiovascular risk factors have relied on data aggregated to counties. Herein, we provide the first description of geographic variation in the prevalence of hypertension, diabetes mellitus, and smoking within and across US counties. METHODS AND RESULTS: We conducted a cross-sectional analysis of baseline risk factor measurements and latitude/longitude of participant residence collected from 2003 to 2007 in the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Of the 30 239 participants, all risk factor measurements and location data were available for 28 887 (96%). The mean (±SD) age of these participants was 64.8(±9.4) years; 41% were black; 55% were female; 59% were hypertensive; 22% were diabetic; and 15% were current smokers. In logistic regression models stratified by race, the median(range) predicted prevalence of the risk factors were as follows: for hypertension, 49% (45%-58%) among whites and 72% (68%-78%) among blacks; for diabetes mellitus, 14% (10%-20%) among whites and 31% (28%-41%) among blacks; and for current smoking, 12% (7%-16%) among whites and 18% (11%-22%) among blacks. Hypertension was most prevalent in the central Southeast among whites, but in the west Southeast among blacks. Diabetes mellitus was most prevalent in the west and central Southeast among whites but in south Florida among blacks. Current smoking was most prevalent in the west Southeast and Midwest among whites and in the north among blacks. CONCLUSIONS: Geographic disparities in prevalent hypertension, diabetes mellitus, and smoking exist within states and within counties in the continental United States, and the patterns differ by race.

Inflammatory Markers and Outcomes After Lacunar Stroke: Levels of Inflammatory Markers in Treatment of Stroke Study.

BACKGROUND AND PURPOSE: We hypothesized that concentrations of interleukin 6 (IL-6), serum amyloid A, tumor necrosis factor-α receptor 1, CD40 ligand, and monocyte chemoattractant protein 1 would predict recurrent ischemic stroke and major vascular events after recent lacunar stroke. METHODS: Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within the Secondary Prevention of Small Subcortical Strokes (SPS3) study, a Phase III trial in patients with recent lacunar stroke. Crude and Adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CI) for recurrence risks. RESULTS: Among 1244 patients with lacunar stroke (mean age, 63.3±10.8 years), there were 115 major vascular events (stroke, myocardial infarction, and vascular death). The risk of major vascular events increased with elevated concentrations of both tumor necrosis factor-α receptor 1 (adjusted HR per SD, 1.21; 95% CI, 1.05-1.41; P=0.01) and IL-6 (adjusted HR per SD, 1.10; 95% CI, 1.02-1.19; P=0.008). Compared with the bottom quartile (tumor necrosis factor-α receptor 1 <2.24 ng/L), those in the top quartile of tumor necrosis factor-α receptor 1 (>3.63 ng/L) were at twice the risk of major vascular events after adjusting for demographics (partially adjusted HR, 1.98; 95% CI, 1.11-3.52), though the effect attenuated after adjusting for other risk factors and statin use (adjusted HR, 1.68; 95% CI, 0.93-3.04). Serum amyloid A, CD40 ligand, and monocyte chemoattractant protein 1 were not associated with prognosis. CONCLUSIONS: Among recent lacunar stroke patients, IL-6 and TNF receptor concentrations predict risk of recurrent vascular events, and they are associated with the effect of antiplatelet therapies. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

Differences in the role of black race and stroke risk factors for first vs. recurrent stroke.

OBJECTIVES: To assess whether black race and other cerebrovascular risk factors have a differential effect on first vs. recurrent stroke events. METHODS: Estimate the differences in the magnitude of the association of demographic (age, back race, sex) or stroke risk factors (hypertension, diabetes, cigarette smoking, atrial fibrillation, left ventricular hypertrophy, or heart disease) for first vs. recurrent stroke from a longitudinal cohort study of 29,682 black or white participants aged 45 years and older. RESULTS: Over an average 6.8 years follow-up, 301 of 2,993 participants with a previous stroke at baseline had a recurrent stroke, while 818 of 26,689 participants who were stroke-free at baseline had a first stroke. Among those stroke-free at baseline, there was an age-by-race interaction (p = 0.0002), with a first stroke risk 2.70 (95% confidence interval: 1.86-3.91) times greater for black than white participants at age 45, but no racial disparity at age 85 (hazard ratio = 0.91; 95% confidence interval: 0.70-1.18). In contrast, there was no evidence of a higher risk of recurrent stroke at any age for black participants (p > 0.05). The association of traditional stroke risk factors was generally similar for first and recurrent stroke. CONCLUSION: The association of age and black race differs substantially on first vs. recurrent stroke risk, with risk factors playing a similar role.

Environmental Tobacco Smoke and Atrial Fibrillation: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study.

OBJECTIVE: This study examines the association between environmental tobacco smoke (ETS) exposure and atrial fibrillation (AF). METHODS: We examined the cross-sectional association between ETS exposure and AF in 12,021 participants (mean age: 65 ±â€Š9.9 years; 60% women; 40% blacks) from the REasons for Geographic And Racial Differences in Stroke study who self-identified as never smokers between 2003 and 2007. RESULTS: A total of 2503 (21%) participants reported ETS exposure. In a multivariate logistic regression model adjusted for sociodemographics and potential confounders, ETS exposure was significantly associated with AF (odds ratio = 1.27, 95% confidence interval = 1.08, 1.50). CONCLUSIONS: Our findings suggest that the harmful effects of ETS exposure extend to sustained arrhythmias such as AF.

Secondhand Smoke Exposure and Stroke: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

INTRODUCTION: Stroke is a major public health concern worldwide given the associated morbidity and mortality. Smoking is a risk factor for stroke, but the relationship between secondhand smoke (SHS) exposure and stroke has been inconsistent to date. The aim of the current study was to examine the association of SHS exposure and risk of stroke and its subtypes (ischemic and hemorrhagic stroke) among nonsmokers. METHODS: Demographic and clinical characteristics were compared by SHS exposure status for African American and white nonsmokers aged ≥45 years in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study in 2014. Hazard ratios (HRs) and corresponding 95% CIs were calculated by Cox proportional hazards models to assess the relationship between SHS exposure and stroke risk. RESULTS: Of the 21,743 participants (38% African American, 45% male), SHS exposure in the past year was reported by 23%. Compared with those without SHS exposure, exposed participants were more likely to be female, white, younger, and reside with a smoker (all p<0.001). A total of 428 incident strokes were observed from April 2003 to March 2012 during a mean follow-up of 5.6 years. The risk of overall stroke was increased 30% among those with SHS exposure after adjustment for other stroke risk factors (95% CI=2%, 67%). This relationship appeared to be driven by ischemic strokes. CONCLUSIONS: SHS exposure is independently associated with an increased risk of stroke. Future studies are needed to confirm these findings and examine the role of long-term effects of SHS exposure on stroke outcomes.

Geographic region and racial variations in polypharmacy in the United States.

PURPOSE: Medications can have unintended effects. High medication use populations may benefit from increased regimen oversight. Limited knowledge exists concerning racial and regional polypharmacy variation. We estimated total medication distributions (excluding supplements) of American black and white adults and assessed racial and regional polypharmacy variation. METHODS: REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort data (n = 30,239 U.S. blacks and whites aged ≥45 years) were analyzed. Home pill bottle inspections assessed the last two weeks' medications. Polypharmacy (≥8 medications) was determined by summing prescription and/or over-the-counter ingredients. Population-weighted logistic regression assessed polypharmacy's association with census region, race, and sex. RESULTS: The mean ingredient number was 4.12 (standard error = 0.039), with 15.7% of REGARDS using 8 ingredients or more. In crude comparisons, women used more medications than men, and blacks and whites reported similar mean ingredients. A cross-sectional, logistic model adjusting for demographics, socioeconomics, and comorbidities showed increased polypharmacy prevalence in whites versus blacks (OR [95% CI]: 0.63, [0.55-0.72]), women (1.94 [1.68-2.23]), and Southerners (broadly Southeasterners and Texans; 1.48 [1.17-1.87]) versus Northeasterners (broadly New England and upper Mid-Atlantic). Possible limitations include polypharmacy misclassification and model misspecification. CONCLUSION: Polypharmacy is common. Race and geography are associated with polypharmacy variation. Further study of underlying factors explaining these differences is warranted.

American Heart Association's Life's Simple 7 and risk of venous thromboembolism: the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.

BACKGROUND: The American Heart Association's Life's Simple 7 metric is being used to track the population's cardiovascular health (CVH) toward a 2020 goal for improvement. The metric includes body mass index (BMI), blood pressure, cholesterol, glucose, physical activity (PA), cigarette smoking, and diet. We hypothesized a lower risk of venous thromboembolism (VTE) with favorable Life's Simple 7 scores. METHODS AND RESULTS: REGARDS recruited 30,239 black and white participants ≥45 years of age across the United States in 2003-2007. A 14-point summary score for Life's Simple 7 classified participants into inadequate (0 to 4 points), average (5 to 9 points), and optimal (10 to 14 points) categories. Hazard ratios (HRs) of incident VTE were calculated for these categories, adjusting for age, sex, race, income, education, and region of residence. For comparison, HRs of VTE were calculated using the Framingham 10-year coronary risk score. There were 263 incident VTE cases over 5.0 years of follow-up; incidence rates per 1000 person-years declined from 2.9 (95% confidence interval [CI], 2.3 to 3.7) among those in the inadequate category to 1.8 (95% CI, 1.4 to 2.4) in the optimal category. Compared to the inadequate category, participants in the average category had a 38% lower VTE risk (95% CI, 11 to 57) and participants in the optimal category had a 44% lower risk (95% CI, 18 to 62). The individual score components related to lower VTE risk were ideal PA and BMI. There was no association of Framingham Score with VTE. CONCLUSIONS: Life's Simple 7, a CVH metric, was associated with reduced VTE risk. Findings suggest that efforts to improve the population's CVH may reduce VTE incidence.

The American Heart Association Life's Simple 7 and incident cognitive impairment: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

BACKGROUND: Life's Simple 7 is a new metric based on modifiable health behaviors and factors that the American Heart Association uses to promote improvements to cardiovascular health (CVH). We hypothesized that better Life's Simple 7 scores are associated with lower incidence of cognitive impairment. METHODS AND RESULTS: For this prospective cohort study, we included REasons for Geographic And Racial Differences in Stroke (REGARDS) participants aged 45+ who had normal global cognitive status at baseline and no history of stroke (N=17 761). We calculated baseline Life's Simple 7 score (range, 0 to 14) based on smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and fasting glucose. We identified incident cognitive impairment using a 3-test measure of verbal learning, memory, and fluency obtained a mean of 4 years after baseline. Relative to the lowest tertile of Life's Simple 7 score (0 to 6 points), odds ratios of incident cognitive impairment were 0.65 (0.52, 0.81) in the middle tertile (7 to 8 points) and 0.63 (0.51, 0.79) in the highest tertile (9 to 14 points). The association was similar in blacks and whites, as well as outside and within the Southeastern stroke belt region of the United States. CONCLUSIONS: Compared with low CVH, intermediate and high CVH were both associated with substantially lower incidence of cognitive impairment. We did not observe a dose-response pattern; people with intermediate and high levels of CVH had similar incidence of cognitive impairment. This suggests that even when high CVH is not achieved, intermediate levels of CVH are preferable to low CVH.

Assessing the performance of the Framingham Stroke Risk Score in the reasons for geographic and racial differences in stroke cohort.

BACKGROUND AND PURPOSE: The most well-known stroke risk score is the Framingham Stroke Risk Score (FSRS), which was developed during the higher stroke risk period of the 1990s and has not been validated for blacks. We assessed the performance of the FSRS among participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine whether it is useful in both blacks and whites. METHODS: Expected annualized stroke rates from the FSRS were compared with observed stroke rates overall and within strata defined by FSRS risk factors (age, sex, systolic blood pressure, use of antihypertensive medications, diabetes mellitus, smoking, atrial fibrillation, left ventricular hypertrophy, and prevalent coronary heart disease). RESULTS: Among 27 748 participants stroke-free at baseline, 715 stroke events occurred over 5.6 years of follow-up. FSRS-estimated incidence rates of stroke were 1.6× higher than observed for black men, 1.9× higher for white men, 1.7× higher for black women, and 1.7× higher for white women. This overestimation was consistent among most subgroups of FSRS factors, although the magnitude of overestimation varied by the risk factor assessed. CONCLUSIONS: Although higher FSRS was associated with higher stroke risk, the FSRS overestimated the observed stroke rates in this study, particularly in certain subgroups. This may be because of temporal declines in stroke rates, secular trends in prevention treatments, or differences in populations studied. More accurate estimates of event rates are critical for planning research, including clinical trials, and targeting health-care efforts.