Publications by authors named "Leslie A McClure"

193 Publications

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

Trials 2021 May 2;22(1):319. Epub 2021 May 2.

AJ Drexel Autism Institute, Drexel University, 3020 Market Street, Philadelphia, PA, 19104, USA.

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.
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http://dx.doi.org/10.1186/s13063-021-05286-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091523PMC
May 2021

WeCareAdvisor, an Online Platform to Help Family Caregivers Manage Dementia-Related Behavioral Symptoms: an Efficacy Trial in the Time of COVID-19.

J Technol Behav Sci 2021 Mar 25:1-12. Epub 2021 Mar 25.

Johns Hopkins University, Baltimore, MD USA.

Dementia-related behavioral and psychology symptoms (BPSD) are undertreated and have negative consequences. However, families do not have access to disease information, tailored problem-solving  and effective management strategies, and with COVID-19, are more socially isolated and distressed. To address this dementia care gap, we describe a Phase III efficacy trial testing an online platform, WeCareAdvisor, and design modifications necessitated by COVID-19. WeCareAdvisor provides caregivers with disease information, daily tips, and a systematic approach for behaviors, underlying causes, tailored strategies, and their effectiveness (DICE). The trial will enroll 326 caregivers nationwide, randomly assign them to immediately receive WeCareAdvisor (treatment), or a 3-month waitlist (control) and evaluate short (1- and 3-month) and long-term (6-month) outcomes for caregiver distress with and confidence managing BPSD, and BPSD occurrences. We will also evaluate utilization patterns with different prompting conditions: high-intensity (telephone and email reminders), low-intensity (email reminders), or no reminders to use WeCareAdvisor. COVID-19 necessitated design modifications resulting in greater inclusivity of caregivers from diverse races, ethnicities, and geographic areas. Key modifications include shifting from in-home, in-person interviewing to telephone; adjusting tool functionality from operating on a grant-funded iPad to caregivers' personal internet-capable devices; and expanding recruitment from one metropolitan area to nationwide. Study modifications necessitated by COVID-19 facilitate national outreach, easier tool adoption, and enable more diverse caregivers to participate. This study addresses a critical dementia care need, and design modifications may shorten timeline from efficacy testing to commercialization.
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http://dx.doi.org/10.1007/s41347-021-00204-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994055PMC
March 2021

Relation of Atrial Fibrillation to Cognitive Decline (from the REasons for Geographic and Racial Differences in Stroke [REGARDS] Study).

Am J Cardiol 2021 Mar 6. Epub 2021 Mar 6.

Department of Epidemiology & Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina; Department of Internal Medicine, Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina. Electronic address:

The association of atrial fibrillation (AF) with cognitive function remains unclear, especially among racially/geographically diverse populations. This analysis included 25,980 black and white adults, aged 48+, from the national REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, free from cognitive impairment and stroke at baseline. Baseline AF was identified by self-reported medical history or electrocardiogram (ECG). Cognitive testing was conducted yearly with the Six Item Screener (SIS) to define impairment and at 2-year intervals to assess decline on: animal naming and letter fluency, Montreal Cognitive Assessment (MoCA), Word List Learning (WLL) and Delayed Recall tasks (WLD). Multivariable regression models estimated the relationships between AF and baseline impairment and time to cognitive impairment. Models were adjusted sequentially for age, sex, race, geographic region, and education, then cardiovascular risk factors and finally incident stroke. AF was present in 2,168 (8.3%) participants at baseline. AF was associated with poorer baseline performance on measures of: semantic fluency (p<0.01); global cognitive performance (MoCA, p<0.01); and WLD (p<0.01). During a mean follow-up of 8.06 years, steeper declines in list learning were observed among participants with AF (p<0.03) which remained significant after adjusting for cardiovascular risk factors (p<0.04) and incident stroke (p<0.03). Effect modification by race, sex and incident stroke on AF and cognitive decline were also detected. In conclusion, AF was associated with poorer baseline cognitive performance across multiple domains and incident cognitive impairment in this bi-racial cohort. Additional adjustment for cardiovascular risk factors attenuated these relations with the exception of learning.
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http://dx.doi.org/10.1016/j.amjcard.2021.02.036DOI Listing
March 2021

Correlates of a southern diet pattern in a national cohort study of blacks and whites: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

Br J Nutr 2021 Feb 26:1-7. Epub 2021 Feb 26.

Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.

The Southern dietary pattern, derived within the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, is characterised by high consumption of added fats, fried food, organ meats, processed meats and sugar-sweetened beverages and is associated with increased risk of several chronic diseases. The aim of the present study was to identify characteristics of individuals with high adherence to this dietary pattern. We analysed data from REGARDS, a national cohort of 30 239 black and white adults ≥45 years of age living in the USA. Dietary data were collected using the Block 98 FFQ. Multivariable linear regression was used to calculate standardised beta coefficients across all covariates for the entire sample and stratified by race and region. We included 16 781 participants with complete dietary data. Among these, 34·6 % were black, 45·6 % male, 55·2 % resided in stroke belt region and the average age was 65 years. Black race was the factor with the largest magnitude of association with the Southern dietary pattern (Δ = 0·76 sd, P < 0·0001). Large differences in Southern dietary pattern adherence were observed between black participants and white participants in the stroke belt and non-belt (stroke belt Δ = 0·75 sd, non-belt Δ = 0·77 sd). There was a high consumption of the Southern dietary pattern in the US black population, regardless of other factors, underlying our previous findings showing the substantial contribution of this dietary pattern to racial disparities in incident hypertension and stroke.
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http://dx.doi.org/10.1017/S0007114521000696DOI Listing
February 2021

The Relationship Between Glucose Control and Cognitive Function in People With Diabetes After a Lacunar Stroke.

J Clin Endocrinol Metab 2021 Mar;106(4):e1521-e1528

Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada.

Context: Lacunar strokes and diabetes are risk factors for cognitive dysfunction. Elucidating modifiable risk factors for cognitive dysfunction has great public health implications. One factor may be glycemic status, as measured by glycated hemoglobin (A1c).

Objective: The aim of this study was to assess the relationship between A1c and cognitive function in lacunar stroke patients with diabetes.

Methods: The effect of baseline and follow-up A1c on the baseline and the change in Cognitive Assessment Screening Instrument (CASI) score over time among participants with a median of 2 cognitive assessments (range, 1-5) was examined in 942 individuals with diabetes and a lacunar stroke who participated in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (ClinicalTrials.gov No. NCT00059306).

Results: Every 1% higher baseline A1c was associated with a 0.06 lower standardized CASI z score (95% CI, -0.101 to -0.018). Higher baseline A1c values were associated with lower CASI z scores over time (P for interaction = .037). A 1% increase in A1c over time corresponded with a CASI score decrease of 0.021 (95% CI, -0.0043 to -0.038) during follow-up. All these remained statistically significant after adjustment for age, sex, education, race, depression, hypertension, hyperlipidemia, body mass index, cardiovascular disease, obstructive sleep apnea, diabetic retinopathy, nephropathy insulin use, and white-matter abnormalities.

Conclusion: This analysis of lacunar stroke patients with diabetes demonstrates a relationship between A1c and change in cognitive scores over time. Intervention studies are needed to delineate whether better glucose control could slow the rate of cognitive decline in this high-risk population.
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http://dx.doi.org/10.1210/clinem/dgab022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993572PMC
March 2021

C-reactive protein and risk of cognitive decline: The REGARDS study.

PLoS One 2020 31;15(12):e0244612. Epub 2020 Dec 31.

Departments of Medicine and Pathology & Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington, Vermont, United States of America.

Markers of systemic inflammation are associated with increased risk of cognitive impairment, but it is unclear if they are associated with a faster rate of cognitive decline and whether this relationship differs by race. Our objective was to examine the association of baseline C-reaction protein (CRP) with cognitive decline among a large racially diverse cohort of older adults. Participants included 21,782 adults aged 45 and older (36% were Black, Mean age at baseline 64) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. CRP was measured at baseline and used as a continuous variable or a dichotomous grouping based on race-specific 90th percentile cutoffs. Cognitive measures of memory and verbal fluency were administered every 2 years for up to 12 years. Latent growth curve models evaluated the association of CRP on cognitive trajectories, adjusting for relevant demographic and health factors. We found that higher CRP was associated with worse memory (B = -.039, 95% CI [-.065,-.014]) and verbal fluency at baseline (B = -.195, 95% CI [-.219,-.170]), but not with rate of cognitive decline. After covariate adjustment, the association of CRP on memory was attenuated (B = -.005, 95% CI [-.031,-.021]). The association with verbal fluency at baseline, but not over time, remained (B = -.042, 95% CI [-.067,-.017]). Race did not modify the association between CRP and cognition. Findings suggest that levels of CRP at age 45+, are a marker of cognitive impairment but may not be suitable for risk prediction for cognitive decline.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244612PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774911PMC
March 2021

Prenatal air pollution exposure and neurodevelopment: A review and blueprint for a harmonized approach within ECHO.

Environ Res 2020 Oct 22:110320. Epub 2020 Oct 22.

Department of Environmental Medicine and Public Health, And Pediatrics, Institute for Exposomics Research, Kravis Children's Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Air pollution exposure is ubiquitous with demonstrated effects on morbidity and mortality. A growing literature suggests that prenatal air pollution exposure impacts neurodevelopment. We posit that the Environmental influences on Child Health Outcomes (ECHO) program will provide unique opportunities to fill critical knowledge gaps given the wide spatial and temporal variability of ECHO participants.

Objectives: We briefly describe current methods for air pollution exposure assessment, summarize existing studies of air pollution and neurodevelopment, and synthesize this information as a basis for recommendations, or a blueprint, for evaluating air pollution effects on neurodevelopmental outcomes in ECHO.

Methods: We review peer-reviewed literature on prenatal air pollution exposure and neurodevelopmental outcomes, including autism spectrum disorder, attention deficit hyperactivity disorder, intelligence, general cognition, mood, and imaging measures. ECHO meta-data were compiled and evaluated to assess frequency of neurodevelopmental assessments and prenatal and infancy residential address locations. Cohort recruitment locations and enrollment years were summarized to examine potential spatial and temporal variation present in ECHO.

Discussion: While the literature provides compelling evidence that prenatal air pollution affects neurodevelopment, limitations in spatial and temporal exposure variation exist for current published studies. As >90% of the ECHO cohorts have collected a prenatal or infancy address, application of advanced geographic information systems-based models for common air pollutant exposures may be ideal to address limitations of published research.

Conclusions: In ECHO we have the opportunity to pioneer unifying exposure assessment and evaluate effects across multiple periods of development and neurodevelopmental outcomes, setting the standard for evaluation of prenatal air pollution exposures with the goal of improving children's health.
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http://dx.doi.org/10.1016/j.envres.2020.110320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060371PMC
October 2020

The Diabetes Location, Environmental Attributes, and Disparities Network: Protocol for Nested Case Control and Cohort Studies, Rationale, and Baseline Characteristics.

JMIR Res Protoc 2020 Oct 19;9(10):e21377. Epub 2020 Oct 19.

Department of Population Health, NYU Langone Health, New York, NY, United States.

Background: Diabetes prevalence and incidence vary by neighborhood socioeconomic environment (NSEE) and geographic region in the United States. Identifying modifiable community factors driving type 2 diabetes disparities is essential to inform policy interventions that reduce the risk of type 2 diabetes.

Objective: This paper aims to describe the Diabetes Location, Environmental Attributes, and Disparities (LEAD) Network, a group funded by the Centers for Disease Control and Prevention to apply harmonized epidemiologic approaches across unique and geographically expansive data to identify community factors that contribute to type 2 diabetes risk.

Methods: The Diabetes LEAD Network is a collaboration of 3 study sites and a data coordinating center (Drexel University). The Geisinger and Johns Hopkins University study population includes 578,485 individuals receiving primary care at Geisinger, a health system serving a population representative of 37 counties in Pennsylvania. The New York University School of Medicine study population is a baseline cohort of 6,082,146 veterans who do not have diabetes and are receiving primary care through Veterans Affairs from every US county. The University of Alabama at Birmingham study population includes 11,199 participants who did not have diabetes at baseline from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort study with oversampling of participants from the Stroke Belt region.

Results: The Network has established a shared set of aims: evaluate mediation of the association of the NSEE with type 2 diabetes onset, evaluate effect modification of the association of NSEE with type 2 diabetes onset, assess the differential item functioning of community measures by geographic region and community type, and evaluate the impact of the spatial scale used to measure community factors. The Network has developed standardized approaches for measurement.

Conclusions: The Network will provide insight into the community factors driving geographical disparities in type 2 diabetes risk and disseminate findings to stakeholders, providing guidance on policies to ameliorate geographic disparities in type 2 diabetes in the United States.

International Registered Report Identifier (irrid): DERR1-10.2196/21377.
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http://dx.doi.org/10.2196/21377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605983PMC
October 2020

Forty-Year Shifting Distribution of Systolic Blood Pressure With Population Hypertension Treatment and Control.

Circulation 2020 Oct 5;142(16):1524-1531. Epub 2020 Oct 5.

Department of Biostatistics (G.H.), School of Public Health, University of Alabama at Birmingham.

Background: Hypertension awareness, treatment, and control programs were initiated in the United States during the 1960s and 1970s. Whereas blood pressure (BP) control in the population and subsequent reduced hypertension-related disease risks have improved since the implementation of these interventions, it is unclear whether these BP changes can be generalized to diverse and high-risk populations. This report describes the 4-decade change in BP levels for the population in a high disease risk southeastern region of the United States. The objective is to determine the magnitude of the shift in systolic BP (SBP) among Blacks and Whites from the Southeast between 1960 and 2005 with the assessment of the unique population cohorts.

Methods: A multicohort study design compared BPs from the CHS (Charleston Heart Study) and ECHS (Evans County Heart Study) in 1960 and the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) 4 decades later. The analyses included participants ≥45 years of age from CHS (n=1323), ECHS (n=1842), and REGARDS (n=6294) with the main outcome of SBP distribution.

Results: Among Whites 45 to 54 years of age, the median SBP was 18 mm Hg (95% CI, 16-21 mm Hg) lower in 2005 than 1960. The median shift was a 45 mm Hg (95% CI, 37-51 mm Hg) decline for those ≥75 years of age. The shift was larger for Blacks, with median declines of 38 mm Hg (95% CI, 32-40 mm Hg) at 45 to 54 years of age and 50 mm Hg (95% CI, 33-60 mm Hg) for ages ≥75 years. The 95th percentile of SBP decreased 60 mm Hg for Whites and 70 mm Hg for Blacks.

Conclusions: The results of the current analyses of the unique cohorts in the Southeast confirm the improvements in population SBP levels since 1960. This assessment provides new evidence of improvement in SBP, suggesting that strategies and programs implemented to improve hypertension treatment and control have been extraordinarily successful for both Blacks and Whites residing in a high-risk region of the United States. Severe BP elevations commonly observed in the 1960s have been nearly eliminated, with the current 75th percentile of BP generally less than the 25th percentile of BP in 1960.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.048063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578084PMC
October 2020

Serum magnesium concentration and incident cognitive impairment: the reasons for geographic and racial differences in stroke study.

Eur J Nutr 2021 Apr 31;60(3):1511-1520. Epub 2020 Jul 31.

Department of Obstetrics and Gynecology and Department of Epidemiology, Columbia University Irving Medical Center, New York, NY, USA.

Purpose: To examine the prospective association between serum Mg level and the incidence of cognitive impairment.

Methods: A random sub-cohort (n = 2063) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort was included in this study. Baseline serum Mg concentration was measured using inductively coupled plasma mass spectrometry. According to the current reference interval of serum magnesium (0.75-0.95 mmol/L), we classified participants below the interval as Level 1 and used it as the referent. The rest of the study population were equally divided into three groups, named Level 2 to 4. Incident cognitive impairment was identified using the Six-Item Screener. Multivariable-adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using logistic regression models.

Results: After adjustment for potential confounders, an inverse threshold association between serum Mg level and incident cognitive impairment was observed. Compared to those with hypomagnesemia (Level 1: < 0.75 mmol/L), the relative odds of incident cognitive impairment was reduced by 41% in the second level [OR (95% CI) = 0.59 (0.37, 0.94)]; higher serum Mg level did not provide further benefits [Level 3 and 4 versus Level 1: OR (95% CI) = 0.54 (0.34, 0.88) and 0.59 (0.36, 0.96), P for linear trend = 0.08].

Conclusions: Findings from this prospective study suggest that sufficient Mg status within the normal range may be beneficial to cognitive health in the US general population.
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http://dx.doi.org/10.1007/s00394-020-02353-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854858PMC
April 2021

Injuries on the Youth Soccer (Football) Field: Do Additional Referees Reduce Risk? Randomized Crossover Trial.

J Pediatr Psychol 2020 08;45(7):759-766

Department of Epidemiology and Biostatistics, Drexel University.

Objective: Youth soccer injury can be prevented through various means, but few studies consider the role of referees. Following previous research suggesting children take fewer risks when supervised intensely, this randomized crossover trial evaluated whether risky play and injuries decrease under supervision from three referees instead of one referee.

Methods: Youth soccer clubs serving a metropolitan U.S. area participated. Boys' and girls' clubs at under age 10 (U10) and under age 11 (U11) levels were randomly assigned such that when the same clubs played each other twice in the same season, they played once with one referee and once with three referees. A total of 98 games were videotaped and subsequently coded to obtain four outcomes: collisions between players, aggressive fouls (involving physical player-to-player contact) called by the referee(s) on the field, aggressive fouls judged by trained coders, and injuries requiring adult attention or play stoppage.

Results: Poisson mixed model results suggest players in the 98 games committed fewer aggressive fouls, as identified independently by referees (rate ratio [RR] 0.58; 95% confidence interval [CI] 0.35-0.96) and by researchers (RR 0.67; 95% CI 0.50-0.90), when there were three referees versus one referee. Collisions (RR 0.98; 95% CI 0.86-1.12) and injury rates (RR 1.15; 95% CI 0.60-2.19) were similar across conditions.

Conclusion: When the same youth soccer clubs played with three referees rather than one, they committed fewer aggressive fouls. More intense supervision created better rule adherence. Injury rates were unchanged with increased supervision. Results raise questions concerning whether financial investment in additional referees on youth soccer fields yields safety benefits.
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http://dx.doi.org/10.1093/jpepsy/jsaa050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381189PMC
August 2020

Functional health and white matter hyperintensities as effect modifiers of blood pressure-lowering on cognitive function and vascular events in older Secondary Prevention of Small Subcortical Strokes trial participants.

J Hypertens 2020 08;38(8):1578-1585

Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California, USA.

Objective: To determine whether cerebral small vessel disease or disability modify the effect of SBP treatment on cognitive and vascular outcomes in older patients with recent lacunar stroke.

Methods: Participants aged at least 65 years of the Secondary Prevention of Small Subcortical Strokes Trial were randomized to a higher (130-149 mmHg) or lower (<130 mmHg) SBP target. The primary outcome was change in cognitive function (Cognitive Abilities Screening Instrument); secondary outcomes were incident mild cognitive impairment, stroke, major vascular events (all-stroke, myocardial infarction), and all-cause death. Results were stratified by severity of white matter hyperintensities (WMH; none/mild, moderate, severe) on baseline MRI, and by disability (no vs. at least one limitation in activities of daily living).

Results: One thousand, two hundred and sixty-three participants (mean age 73.8 ± 5.9 years, 40% women) were included. Participants with severe WMH or disability had worse cognitive function at baseline and after a mean follow-up of 3.9 years. No significant interactions existed between treatment group and effect modifiers (WMH, disability) for change in cognitive function (P for interaction 0.42 and 0.66, respectively). A lower SBP target appeared more beneficial among those with worse WMH burden for vascular outcomes (P for interaction = 0.01 for stroke and 0.03 for major vascular events).

Conclusion: There was no difference in the effect of lowering SBP to less than 130 mmHg on cognitive function by cerebral small vessel disease or disability among older adults with a history of lacunar stroke. Those with evidence of small vessel disease may derive greater benefit from lower SBP on prevention of subsequent vascular events.

Trial Registration: Clinicaltrials.gov Identifier: NCT00059306.
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http://dx.doi.org/10.1097/HJH.0000000000002440DOI Listing
August 2020

Assessing the spatial heterogeneity in black-white differences in optimal cardiovascular health and the impact of individual- and neighborhood-level risk factors: The Multi-Ethnic Study of Atherosclerosis (MESA).

Spat Spatiotemporal Epidemiol 2020 06 7;33:100332. Epub 2020 Feb 7.

Department of Epidemiology & Biostatistics, Dornsife School of Public Health, Drexel University, 3215 Market Street, Philadelphia, PA 19104, USA. Electronic address:

Racial disparities in cardiovascular health (CVH) continue to remain a public health concern in the United States. We use unique population-based data from the Multi-Ethnic Study of Atherosclerosis cohort to explore the black-white differences in optimal CVH. Utilizing geographically weighted regression methods, we assess the spatial heterogeneity in black-white differences in optimal CVH and the impact of both individual- and neighborhood-level risk factors. We found evidence of significant spatial heterogeneity in black-white differences that varied within and between the five sites. Initial models showed decreased odds of optimal CVH for blacks that ranged from 60% to 70% reduced odds - with noticeable variation of these decreased odds within each site. Adjusting for risk factors resulted in reductions in the black-white differences in optimal CVH. Further understanding of the reasons for spatial heterogeneities in black-white differences in nationally representative cohorts may provide important clues regarding the drivers of these differences.
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http://dx.doi.org/10.1016/j.sste.2020.100332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205896PMC
June 2020

Exploring the Spatial Patterning in Racial Differences in Cardiovascular Health Between Blacks and Whites Across the United States: The REGARDS Study.

J Am Heart Assoc 2020 05 28;9(9):e016556. Epub 2020 Apr 28.

Department of Epidemiology and Biostatistics Dornsife School of Public Health Drexel University Philadelphia PA.

Background Cardiovascular health (CVH) disparities between blacks and whites have persisted in the United States for some time, and although there have been remarkable improvements in addressing cardiovascular disease, it still remains the leading cause of death in the United States. In addition, well-documented disparities are unfortunately widening incidence gaps across certain regions of the United States. Our focus was on answering the following questions: (1) How much spatial heterogeneity exists in the racial differences in CVH between blacks and whites across this country? and (2) Is the spatial heterogeneity in the racial differences significantly explained by living in the Stroke Belt? Methods and Results To explore the spatial patterning in the racial differences in CVH between blacks and whites across the country, we used geographically weighted regression methods, which result in local estimates of the racial differences in CVH. Using data from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study, we found significant spatial patterning in these racial differences, even beyond the well-known Stroke Belt and Stroke Buckle. All of the estimated differences indicated blacks consistently having diminishing CVH compared with whites, where this difference was largely noted in pockets of the Stroke Belt and Stroke Buckle, in addition to moderate to large disparities noted in the Great Lakes region, portions of the Northeast, and along the West coast. Conclusions Efforts to improve CVH and ultimately reduce disparities between blacks and whites require culturally competent methods, with a strong focus on geography-based interventions and policies.
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http://dx.doi.org/10.1161/JAHA.120.016556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428583PMC
May 2020

Assessing county-level determinants of diabetes in the United States (2003-2012).

Health Place 2020 05 13;63:102324. Epub 2020 Mar 13.

Department of Population Health, NYU School of Medicine, New York, NY, USA.

Using data from the United States Behavioral Risk Factor Surveillance System (2003-2012; N = 3,397,124 adults), we estimated associations between prevalent diabetes and four county-level exposures (fast food restaurant density, convenience store density, unemployment, active commuting). All associations confirmed our a priori hypotheses in conventional multilevel analyses that pooled across years. In contrast, using a random-effects within-between model, we found weak, ambiguous evidence that within-county changes in exposures were associated with within-county change in odds of diabetes. Decomposition revealed that the pooled associations were largely driven by time-invariant, between-county factors that may be more susceptible to confounding versus within-county associations.
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http://dx.doi.org/10.1016/j.healthplace.2020.102324DOI Listing
May 2020

Turning Chutes into Ladders for Women Faculty: A Review and Roadmap for Equity in Academia.

J Womens Health (Larchmt) 2020 05 11;29(5):721-733. Epub 2020 Feb 11.

Department of Environmental Engineering Sciences, Environmental School for Sustainable Infrastructure and the Environment (ESSIE), University of Florida, Gainesville, Florida.

Despite significant progress in recent decades, the recruitment, advancement, and promotion of women in academia remain low. Women represent a large portion of the talent pool in academia, and receive >50% of all PhDs, but this has not yet translated into sustained representation in faculty and leadership positions. Research indicates that women encounter numerous "chutes" that remove them from academia or provide setbacks to promotion at all stages of their careers. These include the perception that women are less competent and their outputs of lesser quality, implicit bias in teaching evaluations and grant funding decisions, and lower citation rates. This review aims to (1) synthesize the "chutes" that impede the careers of women faculty, and (2) provide feasible recommendations, or "ladders" for addressing these issues at all career levels. Enacting policies that function as "ladders" rather than "chutes" for academic women is essential to even the playing field, achieve gender equity, and foster economic, societal, and cultural benefits of academia.
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http://dx.doi.org/10.1089/jwh.2019.8027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247039PMC
May 2020

The effect of time spent outdoors during summer on daily blood glucose and steps in women with type 2 diabetes.

J Behav Med 2020 10 1;43(5):783-790. Epub 2019 Nov 1.

Department of Population Health Sciences, Virginia Tech, Blacksburg, VA, USA.

This study investigated changes in glycemic control following a small increase in time spent outdoors. Women participants with type 2 diabetes (N = 46) wore an iBUTTON temperature monitor and a pedometer for 1 week and recorded their morning fasting blood glucose (FBG) daily. They went about their normal activities for 2 days (baseline) and were asked to add 30 min of time outdoors during Days 3-7 (intervention). Linear mixed effects models were used to test whether morning FBG values were different on days following intervention versus baseline days, and whether steps and/or heat exposure changed. Results were stratified by indicators of good versus poor glycemic control prior to initiation of the study. On average, blood glucose was reduced by 6.1 mg/dL (95% CI - 11.5, - 0.6) on mornings after intervention days after adjusting for age, BMI, and ambient weather conditions. Participants in the poor glycemic control group (n = 16) experienced a 15.8 mg/dL decrease (95% CI - 27.1, - 4.5) in morning FBG on days following the intervention compared to a 1.6 mg/dL decrease (95%CI - 7.7, 4.5) for participants in the good glycemic control group (n = 30). Including daily steps or heat exposure did not attenuate the association between intervention and morning FBG. The present study suggests spending an additional 30 min outdoors may improve glycemic control; however, further examination with a larger sample over a longer duration and determination of mediators of this relationship is warranted.
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http://dx.doi.org/10.1007/s10865-019-00113-5DOI Listing
October 2020

Calcium Intake and Serum Calcium Level in Relation to the Risk of Ischemic Stroke: Findings from the REGARDS Study.

J Stroke 2019 Sep 30;21(3):312-323. Epub 2019 Sep 30.

Department of Epidemiology and Biostatistics, School of Public Health, Indiana University Bloomington, Bloomington, IN, USA.

Background And Purpose: Data on the association between calcium (Ca) and ischemic stroke are sparse and inconsistent. This study aimed to examine Ca intake and serum Ca levels in relation to risk of ischemic stroke.

Methods: The primary analysis included 19,553 participants from the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study. A subcohort was randomly selected to create a case-cohort study (n=3,016), in which serum Ca levels were measured. Ischemic stroke cases were centrally adjudicated by physicians based on medical records. Cox proportional hazards regression for the cohort and weighted Cox proportional hazard regression with robust sandwich estimation method for the case-cohort analysis with adjustment for potential confounders were performed.

Results: During a mean 8.3-year follow-up, 808 incident cases of ischemic stroke were documented. Comparing the highest quintile to the lowest, a statistically significant inverse association was observed between total Ca intake and risk of ischemic stroke (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.55 to 0.95; Plinear-trend=0.183); a restricted cubic spline analysis indicated a threshold effect like non-linear association of total Ca intake with ischemic stroke (Pnon-linear=0.006). In the case-cohort, serum Ca was inversely associated with the risk of ischemic stroke. Compared to the lowest, the highest quintile of serum Ca had a 27% lower risk of ischemic stroke (HR, 0.73; 95% CI, 0.53 to 0.99; Plinear-trend=0.013). Observed associations were mainly mediated by type 2 diabetes, hypertension, and cholesterol.

Conclusion: s These findings suggest that serum Ca has inverse and Ca intake has threshold effect like association with risk of ischemic stroke.
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http://dx.doi.org/10.5853/jos.2019.00542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780017PMC
September 2019

C-reactive protein and stroke risk in blacks and whites: The REasons for Geographic And Racial Differences in Stroke cohort.

Am Heart J 2019 11 12;217:94-100. Epub 2019 Aug 12.

Larner College of Medicine at the University of Vermont, Burlington, VT, USA. Electronic address:

Background: C-reactive protein (CRP) is an inflammatory biomarker used in vascular risk prediction, though with less data in people of color. Blacks have higher stroke incidence and also higher CRP than whites. We studied the association of CRP with ischemic stroke risk in blacks and whites.

Methods: REGARDS, an observational cohort study, recruited and followed 30,239 black and white Americans 45 years and older for ischemic stroke. We calculated hazard ratios and 95% CIs of ischemic stroke by CRP category (<1, 1-3, 3-10, and ≥10 mg/L) adjusted for age, sex and stroke risk factors.

Results: There were 292 incident ischemic strokes among blacks and 439 in whites over 6.9 years of follow-up. In whites, the risk was elevated for CRP in the range from 3 to 10 mg/L and even higher for CRP >10 mg/L, whereas in blacks, an association was only seen for CRP >10 mg/L. Considered as a continuous variable, the risk factor-adjusted hazard ratios per SD higher lnCRP were 1.18 (95% CI 1.09-1.28) overall, 1.14 (95% CI 1.00-1.29) in blacks, and 1.22 (95% CI 1.10-1.35) in whites. Spline regression analysis visually confirmed the race difference in the association.

Conclusions: CRP may not be equally useful in stroke risk assessment in blacks and whites. Confirmation, similar study for coronary heart disease, and identification of reasons for these racial differences require further study.
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http://dx.doi.org/10.1016/j.ahj.2019.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861684PMC
November 2019

Sickle cell trait and risk of cognitive impairment in African-Americans: The REGARDS cohort.

EClinicalMedicine 2019 May-Jun;11:27-33. Epub 2019 May 24.

Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington, VT, United States of America.

Background: Sickle cell anemia may be associated with cognitive dysfunction, and some complications of sickle cell anemia might affect those with sickle cell trait (SCT), so we hypothesized that SCT is a risk factor for cognitive impairment.

Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study enrolled a national cohort of 30,239 white and black Americans from 2003 to 7, who are followed every 6 months. Baseline and annual global cognitive function testing used the Six-Item Screener (SIS), a validated instrument (scores range 0-6; ≤ 4 indicates cognitive impairment). Participants with baseline cognitive impairment and whites were excluded. Logistic regression was used to calculate the association of SCT with incident cognitive impairment, adjusted for risk factors. Linear mixed models assessed multivariable-adjusted change in test scores on a biennially administered 3-test battery measuring learning, memory, and semantic and phonemic fluency.

Findings: Among 7743 participants followed for a median of 7·1 years, 85 of 583 participants with SCT (14·6%) developed incident cognitive impairment compared to 902 of 7160 (12·6%) without SCT. In univariate analysis, the odds ratio (OR) of incident cognitive impairment was 1·18 (95% CI: 0·93, 1·51) for those with SCT vs. those without. Adjustment did not impact the OR. There was no difference in change on 3-test battery scores by SCT status (all  > 0·11).

Interpretation: In this prospective cohort study of black Americans, SCT was not associated with incident cognitive impairment or decline in test scores of learning, memory and executive function.

Funding: National Institutes of Health, American Society of Hematology.
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http://dx.doi.org/10.1016/j.eclinm.2019.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610762PMC
May 2019

Effect of Postural Hypotension on Recurrent Stroke: Secondary Prevention of Small Subcortical Strokes (SPS3) Study.

J Stroke Cerebrovasc Dis 2019 Aug 27;28(8):2124-2131. Epub 2019 May 27.

Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota. Electronic address:

Background: Orthostatic hypotension (OH) has been independently associated with increased risk of stroke and other cardiovascular events. We sought to investigate the relationship between OH at follow-up and recurrent stroke risk in SPS3 (Secondary Prevention of Small Subcortical Strokes) trial patient cohort. This is a retrospective cohort analysis.

Methods: We included all SPS3 trial participants with blood pressure measurements in both sitting and standing position per protocol at baseline, with at least 1 follow-up visit to establish the relationship between OH at follow-up and recurrent stroke risk (primary outcome). Secondary outcomes included major vascular events, myocardial infarction, all-cause mortality, and, ischemic and hemorrhagic stroke subtypes. Participants were classified as having OH at baseline and at each follow-up visit based on a systolic BP decline ≥20 mm Hg or a diastolic BP decline ≥10 mm Hg on position change from sitting to standing. We used Cox proportional hazards regression modeling to compare the risk of outcomes among those with and without OH.

Results: A total of 2275 patients were included with a mean follow up time 3.2 years (standard deviation = 1.6 years). 39% (881/2275) had OH at some point during their follow-up. Of these, 41% (366/881) had orthostatic symptoms accompanying the BP drop. In a fully adjusted model, those with OH had a 1.8 times higher risk of recurrent stroke than those without OH (95% confidence interval: 1.1-3.0). The risk of ischemic stroke, major vascular events, and all-cause mortality was similarly elevated among the OH group.

Conclusion: OH was associated with increased recurrent stroke risk, vascular events, and all-cause death in this large cohort of lacunar stroke patients. Whether minimizing OH in the management of poststroke hypertension in patients with lacunar stroke reduces recurrent stroke risk deserves further study.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679756PMC
August 2019

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.

BMJ Open 2019 05 10;9(5):e027175. Epub 2019 May 10.

Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, Alabama, USA.

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.
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http://dx.doi.org/10.1136/bmjopen-2018-027175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530531PMC
May 2019

Inflammatory cytokines and ischemic stroke risk: The REGARDS cohort.

Neurology 2019 05 19;92(20):e2375-e2384. Epub 2019 Apr 19.

From the Departments of Pathology and Laboratory Medicine (N.S.J., N.A.Z., M.C.) and Medicine (N.A.Z., M.C.), University of Vermont Larner College of Medicine, Burlington; Department of Biometry (P.W.C.), University of Vermont, Burlington; Department of Biostatistics (S.E.J.), University of Alabama at Birmingham; Department of Epidemiology and Biostatistics (L.A.M.), Dornsife School of Public Health, Drexel University, Philadelphia, PA; and Department of Neurology and Rehabilitation Medicine (B.K.), University of Cincinnati College of Medicine, OH.

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; < 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.
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http://dx.doi.org/10.1212/WNL.0000000000007416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598817PMC
May 2019

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

Ann Epidemiol 2019 04 5;32:28-34.e1. Epub 2019 Feb 5.

Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.annepidem.2019.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441374PMC
April 2019

Sex Differences in Risk Factors for Incident Atrial Fibrillation (from the Reasons for Geographic and Racial Differences in Stroke [REGARDS] Study).

Am J Cardiol 2019 05 10;123(9):1453-1457. Epub 2019 Feb 10.

Department of Medicine, Section on Cardiology, Wake Forest School of Medicine, Winston-Salem, North Carolina; Epidemiological Cardiology Research Center (EPICARE), Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina. Electronic address:

We examined whether the sex differences in atrial fibrillation (AF) is related to difference in risk factors leading to AF or due to a differential impact of the same risk factors in 11,806 participants (55.2 % women) from the REGARDS study. Incident AF was ascertained by electrocardiograms and medical history at a follow-up examination. Backwards elimination logistic regression was used to identify AF risk factors in men and women, separately. Over a median follow-up of 9.0years, 588 (11.1%) men and 428 (6.6%) women (p value <0.001) developed AF. Men had a higher risk of AF than women (age and race adjusted odds ratio [OR] [95% confidence interval (CI)]: 1.61 [1.26, 1.75]). Age, white race, height, weight, use of blood pressure lowering medications and history of cardiovascular disease were identified by backward elimination as AF risk factors shared by both sexes. On the other hand, diabetes was an AF risk factor in women but not in men. Among the shared risk factors between men and women, only age showed a stronger association in women than in men [Interaction p-value = 0.003]. Adjustment for the shared risk factors eliminated the sex difference in AF risk (OR [95% CI]: 0.90 [0.74, 1.09]), which was more noticeable in those younger than the median age (62 years) compared to those who were older (interaction p value 0.003). In conclusion, women and men share several AF risk factors, and these shared risk factors explain the sex differences. However, age association with AF differs by sex, and age modifies the associations between sex and other AF risk factors.
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http://dx.doi.org/10.1016/j.amjcard.2019.01.056DOI Listing
May 2019

Cerebral White Matter Hyperintensities, Kidney Function Decline, and Recurrent Stroke After Intensive Blood Pressure Lowering: Results From the Secondary Prevention of Small Subcortical Strokes ( SPS 3) Trial.

J Am Heart Assoc 2019 02;8(3):e010091

1 Kidney Health Research Collaborative University of California, San Francisco San Francisco CA.

Background We aimed to determine whether cerebral white matter hyperintensities ( WMHs ) can distinguish stroke survivors susceptible to rapid kidney function decline from intensive blood pressure ( BP ) lowering. Methods and Results The SPS3 (Secondary Prevention of Small Subcortical Strokes) trial randomized participants with recent lacunar stroke to systolic BP targets of 130 to 149 and <130 mm Hg. We included 2454 participants with WMH measured by clinical magnetic resonance imaging at baseline and serum creatinine measured during follow-up. We tested interactions between BP target and WMH burden on the incidence of rapid kidney function decline (≥30% decrease from baseline estimated glomerular filtration rate at 1-year follow-up) and recurrent stroke. Rapid kidney function decline incidence was 11.0% in the lower- BP -target arm and 8.1% in the higher-target arm (odds ratio=1.40; 95% CI=1.07-1.84). Odds ratio for rapid kidney function decline between lower- and higher-target groups ranged from 1.26 in the lowest WMH tertile (95% CI , 0.80-1.98) to 1.71 in the highest tertile (95% CI , 1.05-2.80; P for interaction=0.65). Overall incidence of recurrent stroke was 7.9% in the lower-target arm and 9.6% in the higher-target arm (hazard ratio=0.80; 95% CI , 0.63-1.03). Hazard ratio for recurrent stroke in the lower-target group was 1.13 (95% CI , 0.73-1.75) within the lowest WMH tertile compared with 0.73 (95% CI , 0.49-1.09) within the highest WMH tertile ( P for interaction=0.04). Conclusions Participants with higher WMH burden appeared to experience greater benefit from intensive BP lowering in prevention of recurrent stroke. By contrast, intensive BP lowering increased the odds of kidney function decline, but WMH burden did not significantly distinguish this risk. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00059306.
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http://dx.doi.org/10.1161/JAHA.118.010091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405594PMC
February 2019

Blood Pressure and Cognitive Decline Over 8 Years in Middle-Aged and Older Black and White Americans.

Hypertension 2019 02;73(2):310-318

Department of Medicine, University of Alabama at Birmingham School of Medicine (V.G.W.).

Although the association between high blood pressure (BP), particularly in midlife, and late-life dementia is known, less is known about variations by race and sex. In a prospective national study of 22 164 blacks and whites ≥45 years without baseline cognitive impairment or stroke from the REGARDS cohort study (Reasons for Geographic and Racial Differences in Stroke), enrolled 2003 to 2007 and followed through September 2015, we measured changes in cognition associated with baseline systolic and diastolic BP (SBP and DBP), as well as pulse pressure (PP) and mean arterial pressure, and we tested whether age, race, and sex modified the effects. Outcomes were global cognition (Six-Item Screener; primary outcome), new learning (Word List Learning), verbal memory (Word List Delayed Recall), and executive function (Animal Fluency Test). Median follow-up was 8.1 years. Significantly faster declines in global cognition were associated with higher SBP, lower DBP, and higher PP with increasing age ( P<0.001 for age×SBP×follow-up-time, age×DBP×follow-up-time, and age×PP×follow-up-time interaction). Declines in global cognition were not associated with mean arterial pressure after adjusting for PP. Blacks, compared with whites, had faster declines in global cognition associated with SBP ( P=0.02) and mean arterial pressure ( P=0.04). Men, compared with women, had faster declines in new learning associated with SBP ( P=0.04). BP was not associated with decline of verbal memory and executive function, after controlling for the effect of age on cognitive trajectories. Significantly faster declines in global cognition over 8 years were associated with higher SBP, lower DBP, and higher PP with increasing age. SBP-related cognitive declines were greater in blacks and men.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.12062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450556PMC
February 2019

Verbal fluency in a national sample: Telephone administration methods.

Int J Geriatr Psychiatry 2019 04 18;34(4):578-587. Epub 2019 Jan 18.

Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.

Objectives: Describe novel methods for ascertaining verbal fluency in a large national sample of adults, examine demographic factors influencing performance, and compare scores to studies using in-person assessment.

Methods/design: Participants were from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national, population-based, longitudinal study of stroke in adults aged 45 years and older. Letter and semantic fluency were gathered, using Letter "F" and Animal Naming, via a telephone-based assessment with computer-assisted scoring of digital recordings.

Results: Initial letter and semantic fluency scores were obtained on 18 505 and 18 072 participants, respectively. For both fluency tests, scores were normally distributed. Younger age and more years of education were associated with better performances (p < 0.0001). The mean and standard deviation for matched subgroups, based on age, gender, and education, were quite comparable with scores reported out of samples using an in-person administration format. Telephone-based assessment also allowed for a level of quality control not available via in-person measurement.

Conclusions: Telephone-based assessment of verbal fluency and computer-assisted scoring programs designed for this study facilitated large-scale data acquisition, storage, and scoring of protocols. The resulting scores have similar characteristics to those obtained by traditional methods. These findings extend validation of cognitive assessment methods, using survey research staff and computer-assisted technology for test administration.
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http://dx.doi.org/10.1002/gps.5054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420356PMC
April 2019

The Prevalence of Cognitive Impairment Among Adults With Incident Heart Failure: The "Reasons for Geographic and Racial Differences in Stroke" (REGARDS) Study.

J Card Fail 2019 Feb 22;25(2):130-136. Epub 2018 Dec 22.

Division of General Internal Medicine, Department of Medicine, Weill Cornell Medical College, New York, New York.

Background: Cognitive impairment (CI) is estimated to be present in 25%-80% of heart failure (HF) patients, but its prevalence at diagnosis is unclear. To improve our understanding of cognition in HF, we determined the prevalence of CI among adults with incident HF in the REGARDS study.

Methods And Results: REGARDS is a longitudinal cohort study of adults ≥45 years of age recruited in the years 2003-2007. Incident HF was expert adjudicated. Cognitive function was assessed with the Six-Item Screener. The prevalence of CI among those with incident HF was compared with the prevalence of CI among an age-, sex-, and race-matched cohort without HF. The 436 participants with incident HF had a mean age of 70.3 years (SD 8.9), 47% were female, and 39% were black. Old age, black race, female sex, less education, and anticoagulation use were associated with CI. The prevalence of CI among participants with incident HF (14.9% [95% CI 11.7%-18.6%]) was similar to the non-HF matched cohort (13.4% [11.6%-15.4%]; P < .43).

Conclusions: A total of 14.9% of the adults with incident HF had CI, suggesting that the majority of cognitive decline occurs after HF diagnosis. Increased awareness of CI among newly diagnosed patients and ways to mitigate it in the context of HF management are warranted.
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http://dx.doi.org/10.1016/j.cardfail.2018.12.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377841PMC
February 2019

Sex and Race Differences in the Association of Incident Ischemic Stroke With Risk Factors.

JAMA Neurol 2019 02;76(2):179-186

Department of Medicine, Larner College of Medicine, Colchester, Vermont.

Importance: Race-specific and sex-specific stroke risk varies across the lifespan, yet few reports describe sex differences in stroke risk separately in black individuals and white individuals.

Objective: To examine incidence and risk factors for ischemic stroke by sex for black and white individuals.

Design, Setting, And Participants: This prospective cohort study included participants 45 years and older who were stroke-free from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, enrolled from the continental United States 2003 through 2007 with follow-up through October 2016. Data were analyzed from March 2018 to September 2018.

Exposures: Sex and race.

Main Outcomes And Measures: Physician-adjudicated incident ischemic stroke, self-reported race/ethnicity, and measured and self-reported risk factors.

Results: A total of 25 789 participants (14 170 women [54.9%]; 10 301 black individuals [39.9%]) were included. Over 222 120 person-years of follow-up, 939 ischemic strokes occurred: 159 (16.9%) in black men, 326 in white men (34.7%), 217 in black women (23.1%), and 237 in white women (25.2%). Between 45 and 64 years of age, white women had 32% lower stroke risk than white men (incidence rate ratio [IRR], 0.68 [95% CI, 0.49-0.94]), and black women had a 28% lower risk than black men (IRR, 0.72 [95% CI, 0.52-0.99]). Lower stroke risk in women than men persisted at age 65 through 74 years in white individuals (IRR, 0.71 [95% CI, 0.55-0.94]) but not in black individuals (IRR, 0.94 [95% CI, 0.68-1.30]); however, the race-sex interaction was not significant. At 75 years and older, there was no sex difference in stroke risk for either race. For white individuals, associations of systolic blood pressure (women: hazard ratio [HR], 1.13 [95% CI, 1.05-1.22]; men: 1.04 [95% CI, 0.97-1.11]; P = .099), diabetes (women: HR, 1.84 [95% CI, 1.35-2.52]; men: 1.13 [95% CI, 0.86-1.49]; P = .02), and heart disease (women: HR, 1.76 [95% CI, 1.30-2.39]; men, 1.26 [95% CI, 0.99-1.60]; P = .09) with stroke risk were larger for women than men, while antihypertensive medication use had a smaller association in women than men (women: HR, 1.17 [95% CI, 0.89-1.54]; men: 1.61 [95% CI, 1.29-2.03]; P = .08). In black individuals, there was no evidence of a sex difference for any risk factors.

Conclusions And Relevance: For both races, at age 45 through 64 years, women were at lower stroke risk than men, and there was no sex difference at 75 years or older; however, the sex difference pattern may differ by race from age 65 through 74 years. The association of risk factors on stroke risk differed by race-sex groups. While the need for primordial prevention, optimal management, and control of risk factors is universal across all age, racial/ethnic, and sex groups, some demographic subgroups may require earlier and more aggressive strategies.
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http://dx.doi.org/10.1001/jamaneurol.2018.3862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439952PMC
February 2019