Search

Background Carotid intima‐media thickness (IMT) is a measure of atherosclerosis and a predictor of vascular diseases. Traditional vascular risk factors and genetic variants do not completely explain the variation in carotid IMT. We sought to identify epigenetic factors that may contribute to the remaining carotid IMT variability. Methods and Results An epigenome‐wide association study was performed in 61 Dominican families with 769 individuals. A cytosine nucleotide that precedes a guanine nucleotide methylation in blood‐derived DNA was measured using the Human MethylationEPIC BeadChip. Linear mixed model analyses were performed regressing bifurcation carotid IMT (bIMT) on beta values for cytosine nucleotide that precedes a guanine nucleotide sites, adjusting for covariates, followed by differentially methylated region (DMR) analysis. One‐sample Mendelian randomization analysis was conducted to investigate causal associations between DMRs and bIMT. Twenty‐five DMRs were associated with bIMT (Sidak P

Strategies to prevent or delay Alzheimer's disease and related dementias (AD/ADRD) are urgently needed, and blood pressure (BP) management is a promising strategy. Yet the effects of different BP control strategies across the life course on AD/ADRD are unknown. Randomized trials may be infeasible due to prolonged follow-up and large sample sizes. Simulation analysis is a practical approach to estimating these effects using the best available existing data. However, existing simulation frameworks cannot estimate the effects of BP control on both dementia and cardiovascular disease. This manuscript describes the design principles, implementation details, and population-level validation of a novel population-health microsimulation framework, the MIchigan ChROnic Disease SIMulation (MICROSIM), for The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP-COG) study of the effect of BP levels over the life course on dementia and cardiovascular disease. MICROSIM is an agent-based Monte Carlo simulation designed using computer programming best practices. MICROSIM estimates annual vascular risk factor levels and transition probabilities in all-cause dementia, stroke, myocardial infarction, and mortality in a nationally representative sample of US adults 18+ using the National Health and Nutrition Examination Survey (NHANES). MICROSIM models changes in risk factors over time, cognition and dementia using changes from a pooled dataset of individual participant data from 6 US prospective cardiovascular cohort studies. Cardiovascular risks were estimated using a widely used risk model and BP treatment effects were derived from meta-analyses of randomized trials. MICROSIM is an extensible, open-source framework designed to estimate the population-level impact of different BP management strategies and reproduces US population-level estimates of BP and other vascular risk factors levels, their change over time, and incident all-cause dementia, stroke, myocardial infarction, and mortality.

Background Guideline‐based hypertension management is integral to the prevention of stroke. We examine trends in antihypertensive medications prescribed after stroke and assess how well a prescriber's blood pressure (BP) medication choice adheres to clinical practice guidelines (BP‐guideline adherence). Methods and Results The FSR (Florida Stroke Registry) uses statewide data prospectively collected for all acute stroke admissions. Based on established guidelines, we defined optimal BP‐guideline adherence using the following hierarchy of rules: (1) use of an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker as first‐line antihypertensive among diabetics; (2) use of thiazide‐type diuretics or calcium channel blockers among Black patients; (3) use of beta blockers among patients with compelling cardiac indication; (4) use of thiazide, angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker, or calcium channel blocker class as first line in all others; (5) beta blockers should be avoided as first line unless there is a compelling cardiac indication. A total of 372 254 cases from January 2010 to March 2020 are in the FSR with a diagnosis of acute ischemic stroke, hemorrhagic stroke, transient ischemic attack, or subarachnoid hemorrhage; 265 409 with complete data were included in the final analysis. Mean age was 70±14 years; 50% were women; and index stroke subtypes were 74% acute ischemic stroke, 11% intracerebral hemorrhage, 11% transient ischemic attack, and 4% subarachnoid hemorrhage. BP‐guideline adherence to each specific rule ranged from 48% to 74%, which is below quality standards of 80%, and was lower among Black patients (odds ratio, 0.7 [95% CI, 0.7–0.83]; P

OBJECTIVES:. Temporal trends and factors associated with the withdrawal of life-sustaining therapy (WLST) after acute stroke are not well determined. DESIGN:. Observational study (2008–2021). SETTING:. Florida Stroke Registry (152 hospitals). PATIENTS:. Acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) patients. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Importance plots were performed to generate the most predictive factors of WLST. Area under the curve (AUC) for the receiver operating curve were generated for the performance of logistic regression (LR) and random forest (RF) models. Regression analysis was applied to evaluate temporal trends. Among 309,393 AIS patients, 47,485 ICH patients, and 16,694 SAH patients; 9%, 28%, and 19% subsequently had WLST. Patients who had WLST were older (77 vs 70 yr), more women (57% vs 49%), White (76% vs 67%), with greater stroke severity on the National Institutes of Health Stroke Scale greater than or equal to 5 (29% vs 19%), more likely hospitalized in comprehensive stroke centers (52% vs 44%), had Medicare insurance (53% vs 44%), and more likely to have impaired level of consciousness (38% vs 12%). Most predictors associated with the decision to WLST in AIS were age, stroke severity, region, insurance status, center type, race, and level of consciousness (RF AUC of 0.93 and LR AUC of 0.85). Predictors in ICH included age, impaired level of consciousness, region, race, insurance status, center type, and prestroke ambulation status (RF AUC of 0.76 and LR AUC of 0.71). Factors in SAH included age, impaired level of consciousness, region, insurance status, race, and stroke center type (RF AUC of 0.82 and LR AUC of 0.72). Despite a decrease in the rates of early WLST (< 2 d) and mortality, the overall rates of WLST remained stable. CONCLUSIONS:. In acute hospitalized stroke patients in Florida, factors other than brain injury alone contribute to the decision to WLST. Potential predictors not measured in this study include education, culture, faith and beliefs, and patient/family and physician preferences. The overall rates of WLST have not changed in the last 2 decades.

Acute ischemic stroke impacts men and women differently. Here, the authors show how different lesion patterns in men and women are linked to the extent of stroke severity.

Background purposeA substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort.Materials and methodsAnalyses relied upon imaging and clinical data from the international MRI-GENIE study. Imaging data comprised both Fluid-attenuated inversion recovery (FLAIR) for white matter hyperintensity (WMH) burden estimation and diffusion-weighted imaging (DWI) sequences for the assessment of acute stroke lesions. The initial step featured the systematic evaluation of occurrences of MAL within one and several vascular supply territories. Associations between MAL and important imaging and clinical characteristics were subsequently determined. The interaction effect between single and multiple lesion status and lesion volume was estimated by means of Bayesian hierarchical regression modeling for both stroke severity and functional outcome.ResultsWe analyzed 2,466 patients (age = 63.4 ± 14.8, 39% women), 49.7% of which presented with a single lesion. Another 37.4% experienced MAL in a single vascular territory, while 12.9% featured lesions in multiple vascular territories. Within most territories, MAL occurred as frequently as single lesions (ratio ∼1:1). Only the brainstem region comprised fewer patients with MAL (ratio 1:4). Patients with MAL presented with a significantly higher lesion volume and acute NIHSS (7.7 vs. 1.7 ml and 4 vs. 3, pFDR < 0.001). In contrast, patients with a single lesion were characterized by a significantly higher WMH burden (6.1 vs. 5.3 ml, pFDR = 0.048). Functional outcome did not differ significantly between patients with single versus multiple lesions. Bayesian analyses suggested that the association between lesion volume and stroke severity between single and multiple lesions was the same in case of anterior circulation stroke. In case of posterior circulation stroke, lesion volume was linked to a higher NIHSS only among those with MAL.ConclusionMultiple lesions, especially those within one vascular territory, occurred more frequently than previously reported. Overall, multiple lesions were distinctly linked to a higher acute stroke severity, a higher total DWI lesion volume and a lower WMH lesion volume. In posterior circulation stroke, lesion volume was linked to a higher stroke severity in multiple lesions only.

Background We sought to determine recurrent stroke predictors among patients with embolic strokes of undetermined source (ESUS). Methods and Results We applied Cox proportional hazards models to identify clinical features associated with recurrent stroke among participants enrolled in RE‐SPECT ESUS (Randomized, Double‐Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) trial, an international clinical trial evaluating dabigatran versus aspirin for patients with ESUS. During a median follow‐up of 19 months, 384 of 5390 participants had recurrent stroke (annual rate, 4.5%). Multivariable models revealed that stroke or transient ischemic attack before the index event (hazard ratio [HR], 2.27 [95% CI, 1.83–2.82]), creatinine clearance

Carotid plaque is a subclinical measure of atherosclerosis. We have previously shown measures of carotid plaque to be heritable in a sample of 100 Dominican families and found evidence for linkage and association of common variants (CVs) on 7q36, 11p15, 14q32 and 15q23 with plaque presence. Our current study aimed to refine these regions further and identify rare variants (RVs) influencing plaque presence. Therefore, we performed targeted sequencing of the one LOD unit down region on 7q36, 11p15, 14q32 and 15q23 in 12 Dominican families with evidence for linkage to plaque presence. Gene-based RV analyses were performed using the Sequence Association Test for familial data (F-SKAT) under two filtering algorithms; 1. all exonic RVs and 2. non-synonymous RVs. Replication analyses were performed using a sample of 22 Dominican families and 556 unrelated Dominicans with Exome Array data. To identify additional non-synonymous RVs influencing plaque, we looked for co-segregation of RVs with plaque in each of the sequenced families. Our most strongly associated gene with evidence for replication was AMPD3 which showed suggestive association with plaque presence in the sequenced families (exonic RV p = 0.003, nonsynonymous RV p = 0.005) and replication families (exonic RV p = 0.04, nonsynonymous RV p = 0.02). Examination of the sequenced family pedigrees revealed two missense variants on chromosome 11 which co-segregated with plaque presence in one of our families; rs61751342 (located in DENND2B), and rs61760882 (located in RNF141). The rs61751342 missense variant is an eQTL for SCUBE2 in the atrial appendage. Notably, SCUBE2 encodes a protein which interacts with vascular endothelial growth factor (VEGF) receptor 2 to regulate VEGF-induced angiogenesis, thus providing biologic plausibility for this gene in atherosclerosis. In conclusion, using targeted sequencing of previously-identified linkage regions, we have identified suggestive evidence for the role of RVs in carotid plaque pathogenesis.

Low Gray-Scale Median (GSM) index is an ultrasonographic parameter of soft, lipid rich plaque morphology that has been associated with stroke and cardiovascular disease (CVD). We sought to explore the contribution of the modifiable and not-modifiable cardiovascular risk factors (RFs) to vulnerable plaque morphology measured by the low GSM index. A total of 1,030 stroke-free community dwelling individuals with carotid plaques present (mean age, 71.8 ± 9.1; 58% women; 56% Hispanic, 20% Non-Hispanic Black, 22% Non-Hispanic White) were assessed for minimum GSM (min GSM) using high-resolution B-mode carotid ultrasound. Multiple linear regression models were used to evaluate the association between RFs and minGSM after adjusting for sociodemographic characteristics. Within an individual, median plaque number was 2 (IQR: 1–3) and mean plaque number 2.3 (SD: 1.4). Mean minGSM was 78.4 ± 28.7 (IQR: 56–96), 76.3 ± 28.8 in men and 80 ± 28.5 in women; 78.7 ± 29.3 in Hispanics participants, 78.5 ± 27.2 in Non-Hispanic Black participants, and 78.2 ± 29 in Non-Hispanic white participants. In multivariable adjusted model, male sex (β = −5.78, p = 0.007), obesity BMI (β = −6.92, p = 0.01), and greater levels of fasting glucose (β = −8.02, p = 0.02) and LDL dyslipidemia (β = −6.64, p = 0.005) were positively associated with lower minGSM, while presence of glucose lowering medication resulted in a significant inverse association (β = 7.68, p = 0.04). Interaction (with p for interaction

Objective: To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a stroke.Methods: We included 890 patients who survived after an acute ischemic stroke from the MRI-Genetics Interface Exploration (MRI-GENIE) study, for whom data on vascular risk factors (VRFs), including age, sex, atrial fibrillation, diabetes mellitus, hypertension, coronary artery disease, smoking, prior stroke history, as well as acute stroke severity, 3- to−6-month modified Rankin Scale score (mRS), WMH, and brain volumes, were available. We defined the unaccounted WMH (uWMH) burden via modeling of expected WMH burden based on the VRF profile of each individual patient. The association of uWMH and mRS score was analyzed by linear regression analysis. The odds ratios of patients who achieved full functional independence (mRS < 2) in between trichotomized uWMH burden groups were calculated by pair-wise comparisons.Results: The expected WMH volume was estimated with respect to known VRFs. The uWMH burden was associated with a long-term functional outcome (β = 0.104, p < 0.01). Excessive uWMH burden significantly reduced the odds of achieving full functional independence after a stroke compared to the low and average uWMH burden [OR = 0.4, 95% CI: (0.25, 0.63), p < 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), p < 0.01, respectively].Conclusion: The excessive amount of uWMH burden unaccounted for by the traditional VRF profile was associated with worse post-stroke functional outcomes. Further studies are needed to evaluate a lifetime brain injury reflected in WMH unrelated to the VRF profile of a patient as an important factor for stroke recovery and a plausible indicator of brain health.

ObjectiveNeuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of quantitatively describing conventional images, radiomic analyses hold potential for evaluating brain health. We sought to: (1) evaluate radiomics to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and (2) uncover associations between predictive radiomic features and clinical phenotypes.MethodsWe analyzed a multi-site cohort of 4,163 acute ischemic strokes (AIS) patients with T2-FLAIR MR images with total brain and WMH segmentations. Radiomic features were extracted from normal-appearing brain tissue (brain mask–WMH mask). Radiomics-based prediction of personalized WMH burden was done using ElasticNet linear regression. We built a radiomic signature of WMH with stable selected features predictive of WMH burden and then related this signature to clinical variables using canonical correlation analysis (CCA).ResultsRadiomic features were predictive of WMH burden (R2 = 0.855 ± 0.011). Seven pairs of canonical variates (CV) significantly correlated the radiomics signature of WMH and clinical traits with respective canonical correlations of 0.81, 0.65, 0.42, 0.24, 0.20, 0.15, and 0.15 (FDR-corrected p-valuesCV1–6 < 0.001, p-valueCV7 = 0.012). The clinical CV1 was mainly influenced by age, CV2 by sex, CV3 by history of smoking and diabetes, CV4 by hypertension, CV5 by atrial fibrillation (AF) and diabetes, CV6 by coronary artery disease (CAD), and CV7 by CAD and diabetes.ConclusionRadiomics extracted from T2-FLAIR images of AIS patients capture microstructural damage of the cerebral parenchyma and correlate with clinical phenotypes, suggesting different radiographical textural abnormalities per cardiovascular risk profile. Further research could evaluate radiomics to predict the progression of WMH and for the follow-up of stroke patients’ brain health.

Background Less than 40% of acute stroke patients have computed tomography (CT) imaging performed within 25 minutes of hospital arrival. We aimed to examine the race‐ethnic and sex differences in door‐to‐CT (DTCT) ≤25 minutes in the FSR (Florida Stroke Registry). Methods and Results Data were collected from 2010 to 2018 for 63 265 patients with acute ischemic stroke from the FSR and secondary analysis was performed on 15 877 patients with intravenous tissue plasminogen activator‐treated ischemic stroke. Generalized estimating equation models were used to determine predictors of DTCT ≤25. DTCT ≤25 was achieved in 56% of cases of suspected acute stroke, improving from 36% in 2010 to 72% in 2018. Women (odds ratio [OR], 0.90; 95% CI, 0.87–0.93) and Black (OR, 0.88; CI, 0.84–0.94) patients who had strokes were less likely, and Hispanic patients more likely (OR, 1.07; CI, 1.01–1.14), to achieve DTCT ≤25. In a secondary analysis among intravenous tissue plasminogen activator‐treated patients, 81% of patients achieved DTCT ≤25. In this subgroup, women were less likely to receive DTCT ≤25 (0.85, 0.77–0.94) whereas no significant differences were observed by race or ethnicity. Conclusions In the FSR, there was considerable improvement in acute stroke care metric DTCT ≤25 in 2018 in comparison to 2010. However, sex and race‐ethnic disparities persist and require further efforts to improve performance and reduce these disparities.

Background: Gut microbiota may impact cognitive function and decline, though data are limited. This pilot study examines the associations between gut dysbiosis products, plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14), with cognitive decline and immune molecule activation among 40 participants in the longitudinal population-based Northern Manhattan Study. Methods: We selected stroke- and dementia-free participants at baseline with high activation levels of core components of the immune signaling pathways underlying microbiota metabolite-cognitive associations (IL-1, IL-17, TNF). Participants were followed with up to three complete neuropsychological assessments, at least 5 years apart. Results: Elevated sCD14 was associated with high levels of IL-1 pathway activation (p ​

Background: Magnetic resonance imaging (MRI) serves as a cornerstone in defining stroke phenotype and etiological subtype through examination of ischemic stroke lesion appearance and is therefore an essential tool in linking genetic traits and stroke. Building on baseline MRI examinations from the centralized and structured radiological assessments of ischemic stroke patients in the Stroke Genetics Network, the results of the MRI-Genetics Interface Exploration (MRI-GENIE) study are described in this work.Methods: The MRI-GENIE study included patients with symptoms caused by ischemic stroke (N = 3,301) from 12 international centers. We established and used a structured reporting protocol for all assessments. Two neuroradiologists, using a blinded evaluation protocol, independently reviewed the baseline diffusion-weighted images (DWIs) and magnetic resonance angiography images to determine acute lesion and vascular occlusion characteristics.Results: In this systematic multicenter radiological analysis of clinical MRI from 3,301 acute ischemic stroke patients according to a structured prespecified protocol, we identified that anterior circulation infarcts were most prevalent (67.4%), that infarcts in the middle cerebral artery (MCA) territory were the most common, and that the majority of large artery occlusions 0 to 48 h from ictus were in the MCA territory. Multiple acute lesions in one or several vascular territories were common (11%). Of 2,238 patients with unilateral DWI lesions, 52.6% had left-sided infarct lateralization (P = 0.013 for χ2 test).Conclusions: This large-scale analysis of a multicenter MRI-based cohort of AIS patients presents a unique imaging framework facilitating the relationship between imaging and genetics for advancing the knowledge of genetic traits linked to ischemic stroke.

Background Physical exercise and cognitive training have been recommended to improve cognitive outcomes poststroke, but a multifaceted strategy including aerobic, resistance, and cognitive training to facilitate poststroke recovery has not been investigated. We aimed to assess the feasibility, adherence, and safety of a combined aerobic, resistance, and cognitive training intervention (CARET+CTI) after stroke. Methods and Results We prospectively randomized patients presenting with recent stroke to a comparison of a supervised 12‐week CARET+CTI program and a control group receiving sham CARET+CTI. Participants were scheduled for 3 weekly CARET and CTI sessions. All participants underwent pre‐ and postintervention assessments of strength, endurance, and cognition. The primary outcomes were feasibility and adherence, defined as the ratio of scheduled and observed visits, and safety. We enrolled 131 participants, of whom 37 withdrew from the study. There were 17 (20%) withdrawals in the CARET+CTI and 20 (44%) in the control group. The observed‐over‐expected visit ratio was significantly higher in the intervention than in the control group (0.74±0.30 versus 0.54±0.38; P=0.003). A total of 99 adverse events were reported by 59 participants, none of which were serious and related to the intervention. Greater gains in physical, cognitive, and mood outcomes were found in the CARET+CTI group than in the control group, but were not statistically significant after adjustments. Conclusions A CARET+CTI intervention, after stroke, is safe, feasible, and has satisfactory participant adherence over 12 weeks. REGISTRATION URL: https://www.clini​caltr​ials.gov. Unique identifier: NCT02272426.

Estimated glomerular filtration rate (eGFR) is a measure of kidney function used to define chronic kidney disease. Here, Morris et al. perform trans-ethnic genome-wide meta-analyses for eGFR in 312,468 individuals and identify novel loci and downstream putative causal genes.

Increased left ventricular mass (LVM) is an intermediate phenotype for cardiovascular disease (CVD) and a predictor of stroke. Using families from the Dominican Republic, we have previously shown LVM to be heritable and found evidence for linkage to chromosome 12p11. Our current study aimed to further characterize the QTL by sequencing the 1 LOD unit down region in 10 families from the Dominican Republic with evidence for linkage to LVM. Within this region, we tested 5477 common variants [CVs; minor allele frequency (MAF) ≥5%] using the Quantitative Transmission-Disequilibrium Test (QTDT). Gene-based analyses were performed to test rare variants (RVs; MAF < 5%) in 181 genes using the family-based sequence kernel association test. A sample of 618 unrelated Dominicans from the Northern Manhattan Study (NOMAS) and 12 Dominican families with Exome Array data were used for replication analyses. The most strongly associated CV with evidence for replication was rs1046116 (Discovery families P = 9.0 × 10−4; NOMAS P = 0.03; replication families P = 0.46), a missense variant in PKP2. In nonsynonymous RV analyses, PKP2 was one of the most strongly associated genes (P = 0.05) with suggestive evidence for replication in NOMAS (P = 0.05). PKP2 encodes the plakophilin 2 protein and is a desmosomal gene implicated in arrythmogenic right ventricular cardiomyopathy and recently in arrhythmogenic left ventricular cardiomyopathy, which makes PKP2 an excellent candidate gene for LVM. In conclusion, sequencing of our previously reported QTL identified common and rare variants within PKP2 to be associated with LVM. Future studies are necessary to elucidate the role these variants play in influencing LVM.

BACKGROUND:Estimated glomerular filtration rate (eGFR) is routinely utilized as a measure of renal function. While creatinine-based eGFR (eGFRcr) is widely used in clinical practice, the use of cystatin-C to estimate GFR (eGFRcys) has demonstrated superior risk prediction in various populations. Prior studies that derived eGFR formulas have infrequently included high proportions of elderly, African-Americans, and Hispanics. OBJECTIVE:Our objective as to compare mortality risk prediction using eGFRcr and eGFRcys in an elderly, race/ethnically diverse population. DESIGN:The Northern Manhattan Study (NOMAS) is a multiethnic prospective cohort of elderly stroke-free individuals consisting of a total of 3,298 participants recruited between 1993 and 2001, with a median follow-up of 18 years. PARTICIPANTS:We included all Northern Manhattan Study (NOMAS) participants with concurrent measured creatinine and cystatin-C. MAIN MEASURES:The eGFRcr was calculated using the CKD-EPI 2009 equation. eGFRcys was calculated using the CKD-EPI 2012 equations. The performance of each eGFR formula in predicting mortality risk was tested using receiver-operating characteristics, calibration and reclassification. Net reclassification improvement (NRI) was calculated based on the Reynolds 10 year risk score from adjusted Cox models with mortality as an outcome. The primary hypothesis was that eGFRcys would better predict mortality than eGFRcr. RESULTS:Participants (n = 2988) had a mean age of 69±10.2 years and were predominantly Hispanic (53%), overweight (69%), and current or former smokers (53% combined). The mean eGFRcr (74.68±18.8 ml/min/1.73m2) was higher than eGFRcys (51.72±17.2 ml/min/1.73m2). During a mean of 13.0±5.6 years of follow-up, 53% of the cohort had died. The AUC of eGFRcys (0.73) was greater than for eGFRcr (0.67, p for difference

Stroke remains a leading cause of death and disability in the United States. No current treatments exist to promote cognitive recovery in survivors of stroke. A previous study from our laboratory determined that an acute bout of forced treadmill exercise was able to promote cognitive recovery in 3 month old male rats after middle cerebral artery occlusion (MCAo). In this study, we tested the hypothesis that 6 days of intense acute bout of forced treadmill exercise (physical exercise – PE) promotes cognitive recovery in 11–14 month old male rats. We determined that PE was able to ameliorate cognitive deficits as determined by contextual fear conditioning. Additionally, we also tested the hypothesis that PE promotes cognitive recovery in 11–13 month old reproductive senescent female rats. In contrast to males, the same intensity of exercise that decrease cognitive deficits in males was not able to promote cognitive recovery in female rats. Additionally, we determined that exercise did not lessen infarct volume in both male and female rats. There are many factors that contribute to higher stroke mortality and morbidities in women and thus, future studies will investigate the effects of PE in aged female rats to identify sex differences.

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

OBJECTIVES/GOALS: The goal of this project was to assess the scientific impact of Miami CTSI’s Mentored Career Development (KL2) Program using bibliometric tools and network visualization in addition to the traditional metrics used to provide a comprehensive evaluation. METHODS/STUDY POPULATION: Scholarly productivity of KL2 scholars were tracked using REDCap. For bibliometric data analysis and visualization, publications were queried using iCite (NIH Office of Portfolio Analysis) and Web of Science database. A total of 173 publications produced by eight KL2 scholars from 2013-2018 were analyzed and categorized into pre-award, during award, and post-award periods. iCite was used to assess scientific influence and translation. Scientific networks and collaboration were visualized using VOSviewer (Centre for Science and Technology Studies, Leiden University). CTSA Common Metrics were tracked using the Results Based Accountability framework. RESULTS/ANTICIPATED RESULTS: Albeit of modest size, the Miami CTSI’s KL2 Program had significant scientific productivity and impact in its first five years. Our KL2 scholars’ publications were cited twice as frequently as other papers in their fields. Further, 48% of publications post KL2 award were above the NIH 50th percentile and had higher citation impact compared to the average NIH-funded paper; 11% were in the top 10% NIH citation ranking. In contrast, only 20% of the publications pre-KL2 award were above the NIH 50th percentile. The program also promoted research collaboration; network visualizations indicate larger co-authorship and organization networks of KL2 scholars post-award. DISCUSSION/SIGNIFICANCE OF IMPACT: Bibliometric and data visualization approaches helped us better identify trends and gauge effectiveness of the KL2 program. These findings provided useful insight into the scientific influence and impact of our scholars’ work.

OBJECTIVES/GOALS: The objectives of this presentation are to discuss 1) the implementation of Consent to Contact at an Academic Medical Center; 2) the access to lists of potential participants by study teams; and 3) the challenges and adjustments made to the initial conceptualized process. METHODS/STUDY POPULATION: Participant recruitment is critical to the success of all research studies. It is particularly challenging when investigators do not have a patient population from which to recruit. Thus, the University of Miami launched the CTC initiative in 2016 to facilitate study recruitment. Study investigators can request access to a registry of participants who agreed to be contacted and meet the initial study eligibility criteria. A multidisciplinary Operational Committee provides oversight and regulates access to the CTC registry. RESULTS/ANTICIPATED RESULTS: The registry has over 110K patients who have agreed to be contacted for eligible research studies. The demographic distribution of the patients in the registry mirrors the diversity of the UHealth population. As of January 2018, when the registry became available to the research community, 25 study teams from different departments, including the All of Us Research Program, have requested potential participant lists. The process of requesting access to patient lists is adapted to studies’ needs, with particular reference to sensitive populations, such as HIV/AIDS, substance abuse, etc. Results on utilization and satisfaction of the CTC initiative are being collected and will be presented. DISCUSSION/SIGNIFICANCE OF IMPACT: The CTC initiative allows UHealth patients to opt-in to the registry for research studies. The Operational Committee continues to monitor the successful consent of patients to participate in individual research studies and improving the request process.

OBJECTIVES/GOALS: The goal of this project was to a) evaluate the first five years of Miami CTSI’s Pilot Translational and Clinical Studies Program using outcome measures that quantify research productivity augmented by the CTSA Common Metrics; and b) use the results to shape future program management. METHODS/STUDY POPULATION: Pilot Program applicant and awardee demographic data were collected during the first 5-year cycle of the Miami CTSI grant. Projects were categorized into the translation spectrum based on type of research using published guidelines. Research productivity from funded pilot projects were tracked annually using internal institutional grant award databases and external databases such as PubMed and NIH Reporter. CTSA Common Metrics were tracked using the Results Based Accountability framework. Relative Citation Ratio (RCR), NIH percentile and translation impact of pilot project publications were determined using the iCite tool (NIH Office of Portfolio Analysis). RESULTS/ANTICIPATED RESULTS: The Miami CTSI’s Pilot Award Program demonstrated notable success in its first five years. Of the twenty-two projects that were funded during that time period, 45% led to follow-on funding for a total of $17.2M—a strong return on investment of 15:1. Further, 77% of awardees had at least one publication. A total of four patents and 43 publications resulted directly from the funded projects. The mean RCR for all publications was 2.7, weighted RCR was 99.87, and nine papers were been cited by clinical documents. Overall, 63% of the projects were classified as T1/T2 (pre-clinical/clinical research) and 37% as T3/T4 (post-clinical translational research/public health). DISCUSSION/SIGNIFICANCE OF IMPACT: Miami CTSI’s Pilot Award Program demonstrated success in scholarly output, follow on funding, and scientific impact. These results will serve as benchmarks going forward and will allow the CTSI to leverage program strengths in collaborating with other institutional internal award mechanisms.

OBJECTIVES/GOALS: We describe here the implementation of a pilot Quality Improvement (QI) program in clinical research processes in order to facilitate translation from bench to community. This presentation will also discuss challenges encountered by the research teams during the implementation of QI activities. METHODS/STUDY POPULATION: Miami CTSI collaborated with University of Kansas’ CTSA to test the implementation of a QI program for clinical research processes. The program has a duration of 1 year and consists of multi-modal training and coaching sessions with different research teams. Six teams comprising of Principal investigators, clinical coordinators, and regulatory specialists participated in the program based in applied clinical microsystem theory science. Team coaches and teams worked together to assess current processes, test new and improved processes, and standardize and disseminate applicable best practices of the QI program. RESULTS/ANTICIPATED RESULTS: The implementation of QI activities in large clinical research settings poses numerous challenges for the research team. We will present survey results from the coaching sessions and follow on feedback from the different teams involved in the program to implement the QI activities. We will describe the modifications and adjustments made to the original conceptual framework of QI program in order for it to be applicable and feasible for the settings of the University of Miami. We will provide recommendations for other academic clinical research centers that are considering implementing a QI program. DISCUSSION/SIGNIFICANCE OF IMPACT: The successful adaptation of a QI process to implement in academic clinical research settings relies on early engagement of the institution leadership, careful selection of team members, as well as developing communication skills to enhance team dynamics as a clinical research unit.

Background Racial/ethnic disparities in acute stroke care may impact stroke outcomes. We compared outcomes by race/ethnicity among elderly Medicare beneficiaries in hospitals participating in the FL‐PR CReSD (Florida–Puerto Rico Collaboration to Reduce Stroke Disparities) registry with those in hospitals not participating in any quality improvement programs (non‐QI) in Florida and Puerto Rico (PR). Methods and Results The population included fee‐for‐service Medicare beneficiaries age 65+ in Florida and PR, discharged with primary diagnosis of ischemic stroke (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD‐9‐CM], codes 433, 434, 436) in 2010–2013. We used mixed logistic models to assess racial/ethnic differences in outcomes (in‐hospital, 30‐day, and 1‐year mortality, and 30‐day readmission) for CReSD and non‐QI hospitals, adjusted for demographic and clinical characteristics. The study included 62 CReSD hospitals (N=44 013, 84% white, 9% black, 4% Florida Hispanic, 1% PR Hispanic) and 113 non‐QI hospitals (N=14 422, 78% white, 7% black, 5% Florida Hispanic, 8% PR Hispanic). For patients treated at CReSD hospitals, there were no differences in risk‐adjusted in‐hospital mortality by race/ethnicity; blacks had lower 30‐day mortality versus whites (odds ratio, 0.86; 95% confidence interval, 0.77–0.97), but higher 30‐day readmission (hazard ratio, 1.09; 1.00–1.18) and 1‐year mortality (odds ratio, 1.13; 1.04–1.23); Florida Hispanics had lower 30‐day readmission (hazard ratio, 0.87; 0.78–0.98). PR Hispanic and black stroke patients treated at non‐QI hospitals had higher risk‐adjusted in‐hospital, 30‐day and 1‐year mortality, but similar 30‐day readmission versus whites treated in non‐QI hospitals. Conclusions Disparities in outcomes were less common in CReSD than non‐QI hospitals, suggesting the benefits of quality improvement programs, particularly those focusing on racial/ethnic disparities.

BACKGROUND/OBJECTIVES:Inflammatory biomarkers have been associated with stroke and mortality, but inflammation may also have detrimental effects beyond acute events. We hypothesized that serum concentrations of interleukin-6 (IL6) and lipoprotein-associated phospholipase A2 (LpPLA2) were inversely associated with long-term functional decline independently of vascular risk factors, stroke and myocardial infarction (MI) occurring during follow-up. DESIGN:Prospective population based cohort study. SETTING:The Northern Manhattan Study. PARTICIPANTS (INCLUDING THE SAMPLE SIZE):Race/ethnically diverse stroke-free individuals in northern Manhattan aged ≥40 years (n = 3298). INTERVENTION:None. MEASUREMENTS:Annual functional assessments with the Barthel index (BI), for a median of 13 years. BI was analyzed as a continuous variable (range 0-100). Baseline demographics, risk factors, and laboratory studies were collected, including IL6 (n = 1679), LpPLA2 mass (n = 1912) and activity (n = 1937). Separate mixed models estimated standardized associations between each biomarker and baseline functional status and change over time, adjusting for demographics, vascular risk factors, social variables, cognition, and depression measured at baseline, and stroke and MI occurring during follow-up. RESULTS:Mean age was 69 (SD 10) years, 35% were male, 53% Hispanic, 74% hypertensive, and 16-24% diabetic. LogIL6 was associated with decline in BI over time (-0.13 points per year, 95% CI -0.24, -0.02) and marginally with baseline BI (-0.20, 95% CI -0.40, 0.01). LpPLA2 activity levels were associated with baseline BI (-0.36, 95% CI -0.68, -0.04) but not change over time, and LpPLA2 mass levels were not associated with either. CONCLUSION:In this large population-based study, higher serum inflammatory biomarker levels were associated with disability, even when adjusting for baseline covariates and stroke and MI occurring during follow-up.

White matter hyperintensity (WMH) burden is a critically important cerebrovascular phenotype linked to prediction of diagnosis and prognosis of diseases, such as acute ischemic stroke (AIS). However, current approaches to its quantification on clinical MRI often rely on time intensive manual delineation of the disease on T2 fluid attenuated inverse recovery (FLAIR), which hinders high-throughput analyses such as genetic discovery.In this work, we present a fully automated pipeline for quantification of WMH in clinical large-scale studies of AIS. The pipeline incorporates automated brain extraction, intensity normalization and WMH segmentation using spatial priors. We first propose a brain extraction algorithm based on a fully convolutional deep learning architecture, specifically designed for clinical FLAIR images. We demonstrate that our method for brain extraction outperforms two commonly used and publicly available methods on clinical quality images in a set of 144 subject scans across 12 acquisition centers, based on dice coefficient (median 0.95; inter-quartile range 0.94–0.95; p

Background The American Heart Association Life's Simple 7 metric defines ideal cardiovascular health (CVH) on 7 factors: smoking, diet, physical activity, body mass index, blood sugar, blood pressure, and cholesterol. This metric has been used to define optimal brain health, but data relative to subclinical imaging biomarkers of brain aging are lacking. This study examines the association between Life's Simple 7 with white matter hyperintensity volume, silent brain infarcts, and cerebral volume. Methods and Results A subsample of stroke‐free participants from the population‐based Northern Manhattan Study underwent brain magnetic resonance imaging an average of 7 years after baseline. Linear and logistic regression models were constructed to estimate associations between the number of ideal CVH metrics achieved with imaging biomarkers of brain aging, adjusting for sociodemographics. Among 1031 participants (mean age at magnetic resonance imaging=72±8, 40% men, 19% black, 16% white, and 65% Hispanic), no one had ideal status in all 7 factors, 1% had ideal status in 6 factors, 18% in 4 to 5 factors, 30% in 3 factors, 33% in 2 factors, and 18% in 0 to 1 factors. The number of ideal CVH factors achieved was inversely associated with white matter hyperintensity volume (beta per factor=−0.047; P=0.04) and silent brain infarct (odds ratio per factor=0.84; 95% confidence interval=0.72–0.97) and positively associated with cerebral volume (beta per factor=0.300; P=0.002). Conclusions An increasing ideal CVH score was associated with less white matter hyperintensity volume and silent brain infarcts and greater cerebral volumes, supporting the Life's Simple 7 metric as a useful measure to quantify optimal brain health. Monitoring and promoting achievement of Life's Simple 7 ideal CVH factors may improve subclinical and clinical brain health outcomes.

Background and purposeCarotid plaque (CP), carotid intima media thickness (cIMT), and stiffness (STIFF) are pre-clinical markers of atherosclerosis and predictors of cerebrovascular disease (CVD). We sought to investigate whether STIFF is a significant determinant of cIMT and CP, which may provide an insight into the mechanism by which STIFF adds to the risk of CVD.MethodsWe analyzed 876 stroke-free subjects from the Northern Manhattan Study with available ultrasound measures. To obtain the associations with STIFF, we performed multivariable-adjusted regression, negative binomial regression (for CP number), and multinomial logistic regression (for plaque area).ResultsThe mean age was 64 ± 9 years; 63% women and 65% Caribbean Hispanics. The mean cIMT was 0.93 ± 0.9 mm, the mean diastolic diameter 6.24 ± 0.94 mm, and STIFF 8.6 ± 6.2 ln mmHg. Prevalence of CP was 57%, and the mean total plaque area was 22.6 ± 23.0 mm2. STIFF was positively associated with cIMT but not with CP. There was an association between diastolic diameter and thick plaque. For each millimeter increase in diastolic diameter, there was about a 20% increased risk of having thick plaque (vs. no plaque). In longitudinal analyses, each millimeter increase in diastolic diameter was associated with a 37% increased risk of incident plaque.ConclusionIncreased STIFF was associated with increased cIMT and carotid artery dilatation with greater plaque burden. Increased cIMT and plaque burden represent vascular remodeling likely resulting from the two different age-related mechanisms, one that includes diffuse wall thickening (cIMT) with STIFF and another that incorporates focal atherosclerosis (plaque) with luminal dilatation.

[This corrects the article DOI: 10.1371/journal.pone.0191172.].

HYPOTHESIS:We hypothesized that P wave terminal Force in the V1 lead (PTFV1) would be associated with leukoaraiosis and subclinical infarcts, especially cortical infarcts, in a population-based, multi-ethnic cohort. METHODS:PTFV1 was collected manually from baseline electrocardiograms of clinically stroke-free Northern Manhattan Study participants. Investigators read brain MRIs for superficial infarcts, deep infarcts, and white matter hyperintensity volume (WMHV). WMHV was adjusted for head size and log transformed, achieving a normal distribution. Logistic regression models investigated the association of PTFV1 with cortical and with all subclinical infarcts. Linear regression models examined logWMHV. Models were adjusted for demographics and risk factors. RESULTS:Among 1174 participants with PTFV1 measurements, the mean age at MRI was 70 ± 9 years. Participants were 14.4% white, 17.6% black, and 65.8% Hispanic. Mean PTFV1 was 3587.35 ± 2315.62 μV-ms. Of the 170 subclinical infarcts, 40 were cortical. PTFV1 ≥ 5000 μV-ms was associated with WMHV in a fully adjusted model (mean difference in logWMHV 0.15, 95% confidence interval 0.01-0.28). PTFV1 exhibited a trend toward an association with cortical infarcts (unadjusted OR per SD change logPTFV1 1.30, 95% CI 0.94-1.81), but not with all subclinical infarcts. CONCLUSION:Electrocardiographic evidence of left atrial abnormality was associated with leukoaraiosis.

BACKGROUND:Accurate glomerular filtration rate estimation informs drug dosing and risk stratification. Body composition heterogeneity influences creatinine production and the precision of creatinine-based estimated glomerular filtration rate (eGFRcr) in the elderly. We compared chronic kidney disease (CKD) categorization using eGFRcr and cystatin C-based estimated GFR (eGFRcys) in an elderly, racially/ethnically diverse cohort to determine their concordance. METHODS:The Northern Manhattan Study (NOMAS) is a predominantly elderly, multi-ethnic cohort with a primary aim to study cardiovascular disease epidemiology. We included participants with concurrently measured creatinine and cystatin C. eGFRcr was calculated using the CKD-EPI 2009 equation. eGFRcys was calculated using the CKD-EPI 2012 equation. Logistic regression was used to estimate odds ratios and 95% confidence intervals of factors associated with reclassification from eGFRcr≥60ml/min/1.73m2 to eGFRcys65 years, obesity, current smoking, white race, and female sex. CONCLUSIONS:In a large, multiethnic, elderly cohort, we found a highly discrepant prevalence of CKD with eGFRcys versus eGFRcr. Determining the optimal method to estimate GFR in elderly populations needs urgent further study to improve risk stratification and drug dosing.

AIMS:Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS:From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS:We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.

Asymmetry of brain dysfunction may disrupt brain network efficiency. We hypothesized that greater left-right white matter hyperintensity volume (WMHV) asymmetry was associated with functional trajectories.Methods: In the Northern Manhattan Study, participants underwent brain MRI with axial T1, T2, and fluid attenuated inversion recovery sequences, with baseline interview and examination. Volumetric WMHV distribution across 14 brain regions was determined separately by combining bimodal image intensity distribution and atlas based methods. Participants had annual functional assessments with the Barthel index (BI, range 0–100) over a mean of 7.3 years. Generalized estimating equations (GEE) models estimated associations of regional WMHV and regional left-right asymmetry with baseline BI and change over time, adjusted for baseline medical risk factors, sociodemographics, and cognition, and stroke and myocardial infarction during follow-up.Results: Among 1,195 participants, greater WMHV asymmetry in the parietal lobes (−8.46 BI points per unit greater WMHV on the right compared to left, 95% CI −3.07, −13.86) and temporal lobes (−2.48 BI points, 95% CI −1.04, −3.93) was associated with lower overall function. Greater WMHV asymmetry in the parietal lobes (−1.09 additional BI points per year per unit greater WMHV on the left compared to right, 95% CI −1.89, −0.28) was independently associated with accelerated functional decline.Conclusions: In this large population-based study with long-term repeated measures of function, greater regional WMHV asymmetry was associated with lower function and functional decline. In addition to global WMHV, WHMV asymmetry may be an important predictor of long-term functional status.

BackgroundThe effects of white matter hyperintensity volume and subclinical brain infarcts on the risk of incident stroke, its ischemic subtypes, and mortality require further study in diverse samples. Methods and ResultsStroke‐free participants in the Northern Manhattan Study underwent magnetic resonance imaging (N=1287; mean age 71±9 years, 60% women, 15% non‐Hispanic white, 17% non‐Hispanic black, 68% Hispanic) and were followed for a median of 8 years (interquartile range: 6–9 years). Cox models estimated proportional hazards of incident stroke of all types, ischemic stroke (and its subtypes), and mortality and stratified by race/ethnicity. In total 72 participants (6%) had incident strokes and 244 died (19%). In fully adjusted models, those with larger white matter hyperintensity volume had greater risk of all stroke types (hazard ratio [HR]: 1.4; 95% CI, 1.1–1.9), ischemic stroke (HR: 1.3; 95% CI, 1.0–1.8), and cryptogenic stroke (HR: 2.2; 95% CI, 1.1–4.4). White and black but not Hispanic participants had increased stroke risk (P

BackgroundLeft ventricular (LV) hypertrophy and subclinical cerebrovascular disease are early manifestations of cardiac and brain target organ damage caused by hypertension. This study aimed to investigate whether intensive office systolic blood pressure (SBP) control has beneficial effects on LV morphology and function and subclinical cerebrovascular disease in elderly patients with hypertension. Methods and ResultsWe examined 420 patients treated for hypertension without history of heart failure and stroke from the CABL (Cardiovascular Abnormalities and Brain Lesions) study. All patients underwent 2‐dimensional echocardiographic examination and brain magnetic resonance imaging. Subclinical cerebrovascular disease was defined as silent brain infarcts and white matter hyperintensity volume. Patients were divided into 3 groups: SBP

Cerebral small-vessel damage manifests as white matter hyperintensities and cerebral atrophy on brain MRI and is associated with aging, cognitive decline and dementia. We sought to examine the interrelationship of these imaging biomarkers and the influence of hypertension in older individuals. We used a multivariate spatial covariance neuroimaging technique to localize the effects of white matter lesion load on regional gray matter volume and assessed the role of blood pressure control, age and education on this relationship. Using a case-control design matching for age, gender, and educational attainment we selected 64 participants with normal blood pressure, controlled hypertension or uncontrolled hypertension from the Northern Manhattan Study cohort. We applied gray matter voxel-based morphometry with the scaled subprofile model to (1) identify regional covariance patterns of gray matter volume differences associated with white matter lesion load, (2) compare this relationship across blood pressure groups, and (3) relate it to cognitive performance. In this group of participants aged 60–86 years, we identified a pattern of reduced gray matter volume associated with white matter lesion load in bilateral temporal-parietal regions with relative preservation of volume in the basal forebrain, thalami and cingulate cortex. This pattern was expressed most in the uncontrolled hypertension group and least in the normotensives, but was also more evident in older and more educated individuals. Expression of this pattern was associated with worse performance in executive function and memory. In summary, white matter lesions from small-vessel disease are associated with a regional pattern of gray matter atrophy that is mitigated by blood pressure control, exacerbated by aging, and associated with cognitive performance.

Background Few adults have ideal cardiovascular health (CVH). We studied associations of an overall CVH score with subclinical cardiovascular disease and events. We assessed whether associations varied by race/ethnicity. Methods and Results Among 5961 participants in the Multi‐Ethnic Study of Atherosclerosis, components of CVH were measured at baseline, 2000‐2002: systolic blood pressure, total cholesterol, fasting glucose, smoking, physical activity, diet, and body mass index. Levels were classified as ideal (2 points), intermediate (1 point), and poor (0 points) according to American Heart Association definitions. Points were summed to produce a CVH score (0‐7 low, 8‐11 moderate, 12‐14 high). Coronary artery calcium, carotid intima‐media thickness, and left ventricular mass were measured at baseline. Cardiovascular disease was defined as myocardial infarction, coronary heart disease death, resuscitated cardiac arrest, stroke, heart failure, or peripheral artery disease. Follow‐up was 10.3 years. Regression models were used to examine associations of the CVH score with subclinical disease and events, adjusting for age, sex, and education. Analyses were stratified by race/ethnicity. Adults with high or moderate CVH scores had significantly lower odds of coronary artery calcium and lower carotid intima‐media thickness and left ventricular mass than adults with low CVH scores. Adults with high or moderate CVH scores were 67% (95%CI 41% to 82%) and 37% (95%CI 22% to 49%) less likely, respectively, to experience a cardiovascular disease event than adults with low scores. There was no interaction with race/ethnicity. Conclusions There is a graded inverse association between CVH scores and measures of subclinical and overt cardiovascular disease that is similar across race/ethnic groups.

BackgroundRacial‐ethnic disparities in acute stroke care can contribute to inequality in stroke outcomes. We examined race‐ethnic disparities in acute stroke performance metrics in a voluntary stroke registry among Florida and Puerto Rico Get With the Guidelines‐Stroke hospitals. Methods and ResultsSeventy‐five sites in the Florida Puerto Rico Stroke Registry (66 Florida and 9 Puerto Rico) recorded 58 864 ischemic stroke cases (2010–2014). Logistic regression models examined racial‐ethnic differences in acute stroke performance measures and defect‐free care (intravenous tissue plasminogen activator treatment, in‐hospital antithrombotic therapy, deep vein thrombosis prophylaxis, discharge antithrombotic therapy, appropriate anticoagulation therapy, statin use, smoking cessation counseling) and temporal trends. Among ischemic stroke cases, 63% were non‐Hispanic white (NHW), 18% were non‐Hispanic black (NHB), 14% were Hispanic living in Florida, and 6% were Hispanic living in Puerto Rico. NHW patients were the oldest, followed by Hispanics, and NHBs. Defect‐free care was greatest among NHBs (81%), followed by NHWs (79%) and Florida Hispanics (79%), then Puerto Rico Hispanics (57%) (P

Background Cerebral microbleeds (CMBs) represent intracerebral hemorrhages due to amyloid angiopathy or exposure to modifiable risk factors. Few community‐based stroke‐free studies including blacks and Hispanics have been done. Methods and Results The Northern Manhattan Study (NOMAS) is a stroke‐free, racially and ethnically diverse cohort study. Brain MRI was performed in 1290 participants, 925 of whom had available T2* gradient‐recall echo data. We used multivariable logistic regression to examine the association of sociodemographics, vascular risk factors, apolipoprotein E (APOE) genotype, and brain MRI markers with CMB presence and location. The prevalence of CMBs in our cohort was 5%. Of the 46 participants with CMBs, 37% had only deep CMBs, 48% had only lobar CMBs, and 15% had CMBs in both locations. The difference in CMB distribution was not statistically significant across race/ethnic group or APOE genotype. In multivariable analyses, age (OR [95% CI]: 1.09 [1.04, 1.15]) and SBIs (2.58 [1.01, 6.59]) were positively associated with CMB presence, and diabetes medication use was negatively associated (0.25 [0.07, 0.86]). Conclusions CMBs may represent the severity of vascular disease in this racially and ethnically diverse cohort. Larger studies are needed to elucidate the association between diabetes medication use and CMB presence.

BackgroundThe American Heart Association defined target levels for 7 cardiovascular health (CVH) factors: smoking, body mass index, physical activity, diet, blood pressure, cholesterol, and glucose. We hypothesized that a greater number of American Heart Association ideal CVH metrics would be associated with less decline in cognitive performance in our multiethnic population. Methods and ResultsA subsample from the population‐based Northern Manhattan Study underwent repeated neuropsychological testing (mean interval 6±2 years). Domain‐specific Z scores were derived by using factor analysis for the domains of Episodic Memory, Semantic Memory, Executive Function, and Processing Speed, based on initial performance and decline over time. Linear regression models were constructed to examine the relationship between the number of ideal CVH metrics at enrollment with later cognitive performance and decline, adjusting for sociodemographics and magnetic resonance imaging brain markers. Among 1033 participants (mean age at initial cognitive assessment 72±8 years, 39% male, 19% black, 16% white, 65% Hispanic; n=722 with repeat testing), 3% had 0 ideal factors, 15% had 1 factor, 33% had 2 factors, 30% had 3 factors, 14% had 4 factors, 4% had 5 factors, 1% had 6 factors, and 0% had 7 factors. An increasing number of ideal CVH factors was associated with better processing speed at initial assessment and less decline. The association was driven by nonsmoking and glucose. Among those with better cognitive performance at initial assessment, positive associations were observed between the number of ideal CVH factors and less decline in the domains of Executive Function and Episodic Memory. ConclusionsThe number of ideal CVH metrics was associated with less decline in the domains of Processing Speed and, to a lesser extent, of Executive Function and Episodic Memory. Ideal CVH promotion benefits brain health and cognitive aging.