bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP301: Racial and Sex Disparities in Risk Factor Burden Among Young Adults with Intracranial Hemorrhage in the Florida Stroke Registry
Authors: Shoskes Aaron , Zhou Lili , YING HAO , Gardener Hannah , Alkhachroum Ayham , Gordon Perue Gillian , Bustillo Antonio , Koch Sebastian , Marulanda Erika , Gutierrez Carolina , Rundek Tatjana , Romano Jose , Asdaghi Negar
Published: January 2025

Introduction:
While intracranial hemorrhage (ICH) is uncommon in young adults (18-55), its incidence is on the rise. While the reasons for this increase are multifactorial, there is likely a contribution from the known rise in traditional vascular risk factors (VRFs) among the general young adult population. We aimed to examine the prevalence of VRFs among young patients with ICH and evaluate for racial and sex disparities in VRF burden.

Methods:
Data of patients hospitalized with stroke between January 2014 and December 2023 were collected by Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry. Young patients aged 18-55 with a diagnosis of ICH were included and separated into two age groups: 18-35 and 36-55. VRFs included hypertension, diabetes, kidney disease, smoking, drug or alcohol abuse, antithrombotic medication use, and sleep apnea. Polymorbidity was defined as the presence of three or more VRFs.

Results:
9541 young ICH patients were included (39% female, 41% White, 17% Hispanic, 33% non-Hispanic Black), and 1240 (13%) of these patients were aged 18-35. The prevalence of each VRF was higher among patients aged 36-55 vs 18-35 (all p values <0.001) with the exception of kidney disease. Only 48% of patients 18-35 and 20% of patients 36-55 had no VRFs. Black patients with ICH had a significantly higher prevelance of polymorbidity than white or Hispanic patients (19% vs 17% vs 15%, p<0.001) and this disparity was more pronounced among patients aged 18-35 (11% vs 6% vs 3%, p<0.001). Male ICH patients demonstrated higher rates of polymorbidity than females (19% vs 15%, p<0.001). In temporal trends analysis, the prevalence of polymorbidity did not significantly change over the interval in either the 18-35 (p=0.3) or 36-55 (p=0.09) age groups. While the prevalence of hypertension increased in both age groups over the time interval (from 24% to 33% in patients 18-35 and from 65% to 68% in patients 36-55), this was offset by decreases in smoking (from 20% to 9% in patients 18-35 and from 22% to 17% in patients 36-55).

Conclusions:
VRFs are common among young ICH patients, and while the prevalence of hypertension increased during the study interval, the overall burden of traditional risk factors did not significantly change. Our findings highlight the persistent need for primary prevention strategies against ICH among young adults and identify specific at-risk populations that would benefit from targeted interventions.
Abstract WP303: Effect Of Socioeconomic Factors On Prolonged Arrival Time In Acute Ischemic Strokes
Authors: Dubinski Michael , Penckofer Mary , Ackerman Jiyoun , Fang Misa , Khalife Jane , Thon Jesse , Schumacher Hermann , Koneru Manisha , Jovin Tudor , Hanafy Khalid
Published: January 2025

Introduction:
Significant strides have been made in optimizing thrombolysis and thrombectomy for acute ischemic stroke treatment. However, available treatment options and better patient outcomes favor stroke patients with hospital arrivals within earlier time frames relative to symptom onset. Socioeconomic status (SES) may impact arrival times and contribute to disparities in treatment rates. We examined the impact of Social Deprivation Index (SDI) score, a proxy for area SES, and other socioeconomic demographics, on hospital arrival times of thrombectomy patients.

Methods:
Data were retrospectively reviewed for large vessel occlusion acute ischemic stroke adults patients from 2019-2023 who were treated with thrombectomy at a single level 1 trauma center. Patients must have been from the field or presented to an outside hospital first for stroke before transfer; patients with in-hospital strokes were excluded. Prolonged arrival time was defined as more than 6 hours from the approximate last known well time. A multivariable logistic regression with 5-fold cross-validation was performed for prolonged arrival time with clinically or statistically significant covariables, with adjusted odds ratios (aOR) and 95% CI being reported.

Results:
Of 429 patients included, thrombolytic agents were given to 45.3% of early arrivals and to only 3.0% of prolonged arrivals. In the multivariable regression, the two highest SDI quartiles (SDI 50 to <75, aOR: 2.12, 95% CI: 1.11-4.03, p=0.02; SDI 75 to 100, aOR: 2.75, 95% CI: 1.45-5.24, p=0.002) were independently associated with prolonged arrival time. Additionally, both Black (aOR: 2.33, 95% CI: 1.29-4.23, p=0.01) and Hispanic (aOR: 2.98, 95% CI: 1.24-7.13, p=0.01) patients were significantly associated with having prolonged arrival times. The multivariable logistic regression had AUC 0.70 (95% CI: 0.66-0.72), and cross-validation had AUC 0.68 (95% CI: 0.63-0.75).

Conclusion:
Race and SDI are factors significantly associated with presentation time following ischemic stroke symptom onset and, subsequently may impact access to and efficacy of reperfusion therapy. Arrival times may be potentially used as a proxy for assessing efficacy of community-level interventions for mitigating disparities in access to stroke care and improving outcomes.
Abstract WP31: Inhibiting Adrenomedullin signaling to prevent mammalian brain arteriovenous malformation
Authors: Fanelli Kayleigh , Martinez Alfredo , Nielsen Corinne
Published: January 2025

Neurovascular disorders- including stroke, brain aneurysm, and vascular malformations- strike an estimated seven million Americans annually and can lead to vascular pathologies, neurological disability, and death. Brain arteriovenous malformation (bAVM) is a neurovascular disease characterized by abnormally enlarged arteriovenous connections that shunt high-pressure, low-resistance blood flow directly from artery to vein, bypassing the normal capillary network. Research suggests that 95% of bAVMs are sporadic with vast genetic heterogeneity, and current treatments are invasive and not applicable to all patients. There are currently no Food and Drug Administration-approved bAVM treatments, highlighting a critical need for mechanistic-based pharmacological therapies. In our endothelial
Rbpj
-deficient (mutant) mouse model of bAVM, we determined molecular and cellular abnormalities to brain vessels, including increased arteriovenous connections diameter (shunts vs capillaries), abnormal endothelial cell (EC) shape, increased vessel permeability, and altered gene expression in mutant mice compared to controls, contributing to impaired vascular remodeling. Most notably, transcript expression data from RNA-seq and quantitative PCR showed increased
Adrenomedullin
(
AM)
expression, sustained over time, in
Rbpj
-deficient brain ECs compared to controls. Our ChIP-sequencing data identified
AM
as a direct binding target of transcription factor Rbpj, a downstream effector of canonical Notch signaling. Our data, with recent studies that showed increased
AM
expression in human bAVM tissue, suggest
AM
as a potential therapeutic target during bAVM pathogenesis. Utilizing small molecule compound NSC16311 that prevents AM from binding its receptor, our work is testing whether
in vivo
administration of NSC16311 (four experimental cohorts, n = 12) during early bAVM pathogenesis effectively inhibits
AM
signaling and prevents bAVM features by evaluating expression levels of downstream effectors in
AM
signaling and assessing arteriovenous diameter, EC shape (length/width), vascular permeability (10kDa fluorescent dextran injection), and survivability in endothelial
Rbpj
-deficient mice. This study will determine whether the abnormalities observed in Rbpj-deficient brain ECs function, at least in part, through
AM
signaling and will test the therapeutic potential of inhibiting the
AM
signaling pathway to prevent EC abnormalities and bAVM formation.
Abstract WP310: Midlife Vascular Risk Factors, Dementia, and Parkinson's Disease-Dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort
Authors: Johri Mohini , Morrill Valerie , Okine Derrick , Seemiller Joseph , Sullivan Kevin , Rosenthal Liana , Shrestha Srishti , Gottesman Rebecca , Chen Honglei
Published: January 2025

Background:
Vascular risk factors, particularly in midlife, are associated with an increased risk of dementia, and smoking has been inversely associated with Parkinson's disease (PD) risk, but the role of these factors in PD-dementia (PDD) is less clear. This study explores whether midlife vascular risk factors are associated with risk of PDD in the community-based ARIC cohort.

Methods:
ARIC participants were evaluated for vascular risk factors (hypertension, diabetes, hypercholesterolemia, smoking, and obesity) in 1987-1989 (ages 44-64) and followed through 2016. PD cases were identified using participant medications, self-reported physician diagnosis, hospitalization and death surveillance, and PD diagnostic data provided by participants and physicians. Dementia was defined by in-person and phone-based cognitive assessment, informant interviews, and hospitalization codes. PDD was defined as having both a PD and dementia diagnosis, with the PD diagnosis occurring first. We excluded participants with missing covariates, on neuroleptic medications, or with PD or dementia at baseline. Adjusted Cox proportional hazards models examined the associations between midlife vascular risk factors (combined in one model) and incident PDD, PD/no dementia, and dementia/no PD, vs no PD/no dementia. We explored effect modification by race.

Results:
Of 13,875 participants (25% Black, 54% female), 179 developed PD at a mean age of 73.4 yo, 94 devleoped PDD at a mean age of 79.2 yo, and 1,791 developed dementia/no PD at a mean age of 79.7 yo. Midlife current smoking (HR 0.41, 95% CI 0.18-0.95, Figure) was signficantly associated with a lower risk of PDD; other vascular risk factors had nonsignficiant associations. Older age, APOEe4, male sex, and low education were significantly assoiated with an increased risk of PDD. Smoking, diabetes, hypertension, obesity, Black race, age, low education, male sex, and APOEe4 were associated with an increased risk of dementia/no PD. There was effect modification by race for smoking and obesity, which were significant risk factors for dementia/no PD in White but not Black participants (Table).

Conclusions:
Smoking in midlife was significantly associated with a lower rate of PDD vs no PD/no dementia. Other vascular risk factors were not associated with PDD, but demographic associations were similar to dementia. Future studies should evaluate these vascular risk factors over the life course and the mechanisms underlying these associations.
Abstract WP311: Prevalence and In-Hospital Outcomes Associated with Cardiomyopathy Subtypes in Patients with Acute Ischemic Stroke
Authors: McNamara Katelyn , Peyravi Reza , Parikh Ohm , Tirschwell David , Bhatt Deepak , Furie Karen , Kasner Scott , Merkler Alexander , Otite Fadar , Sharma Richa
Published: January 2025

Introduction:
Cardiomyopathy (CM) can occur in patients hospitalized with acute ischemic stroke (AIS). The epidemiology of AIS and concomitant CM subtypes is not well-described.

Methods:
Adult hospitalizations in the National Inpatient Sample (NIS) from 2018-2020 with diagnosis of AIS and concomitant CM were characterized by CM etiologies using International Classification of Diseases-10 codes. Demographic characteristics and clinical outcome rates were computed among patients with each CM subtype. The outcomes of interest are detailed in Table 1. Further statistical analyses within CM etiology subgroups were not performed given that the encoded subgroups were not mutually exclusive.

Results:
Of 1,918,985 weighted AIS hospitalizations, there were 144,875 (7.6%) patients with concomitant CM diagnosis, one-third due to ischemic etiology and two-thirds were non-ischemic (CM etiologies not mutually exclusive, Table 1). Patients with CM etiologies such as ischemic and amyloid-induced CM were older (mean ages 70.5 and 72.3 years, respectively) versus those with peripartum and sarcoidosis-related CM (mean ages 33.5 and 48.5 years, respectively). There were sex differences, as patients with concomitant ischemic CM were more likely to be male (71%) versus those with concomitant stress CM (24.9%). Patients with stress CM (72%) and ischemic CM (68%) identified as White, and those with sarcoid-induced (88%) and peripartum (54%) CM were mostly Black. Intracardiac thrombus was detected in decreasing order by CM subtype: drug-induced (13.6%), alcohol-induced (7.7%), dilated (6.2%), restrictive (5.9%), and ischemic (5.2%). Circulatory support was most common with restrictive CM (2.4% IABP). Thrombolysis use was most frequent in patients with peripartum (18%), dilated (9.3%), drug-induced (8.8%), and ischemic CM (8.2%). EVT rates in decreasing order by CM subtype were: Chagas-associated, wet Beriberi, and sarcoidosis-induced CMs (88-100%), drug-induced (10.1%), and stress-induced (7.7%). Stress-induced CM was associated with highest in-hospital mortality rate (17%) and lowest frequency of routine discharge (18%).

Conclusions:
We describe the epidemiology of CM subtypes among patients hospitalized with AIS, the cardiac and stroke-related procedures that these patients undergo, and their clinical outcomes. Understanding the demographic and in-hospital outcomes specific to each CM etiology may provide insight into multidisciplinary management of this vulnerable population.
Abstract WP316: Association between oral carriage of
Streptococcus mutans
positive for collagen-binding protein Cnm and stroke onset age: A subanalysis of RAMESSES study
Authors: Yamamoto Akimasa , Hattori Yorito , Abe Soichiro , Hosoki Satoshi , Nakazawa Shinsaku , Tonomura Shuichi , Saito Satoshi , Takegami Misa , Nakano Kazuhiko , Ihara Masafumi
Published: January 2025

Background:
We reported that cariogenic bacteria
Streptococcus mutans
expressing a collagen-binding protein Cnm on its bacterial surface is associated with the prevalence of intracerebral hemorrhage in retrospective observational studies. However, a peak age of stroke onset in patients carrying Cnm-expressing
S. mutans
remains unknown.

Methods:
A multicenter, prospective cohort study (RAMESSES:
R
isk
a
ssessment of Cn
m
-positiv
e

S
. mutans

in
s
trok
es
urvivors; UMIN Clinical Trials Registry: UMIN000045559) was initiated in November 2018 with 14 Japanese domestic institutions. The main inclusion criteria were as follows: 1) aged ≥40 years; 2) patients who experienced stroke or transient ischemic attack (TIA) that developed within the past one year, and had old deep intracerebral hemorrhage or at least one deep CMB on T2* weighted brain magnetic resonance imaging. We compared the onset age of the stroke or TIA between the Cnm-expressing
S. mutans
carriers and noncarriers.

Results:
Among 230 participants, the median age was 70 years [62–79], and 63 (27.4%) were women. This cohort included 138 patients with ischemic stroke, 60 patients with hemorrhagic stroke, 23 patients with ischemic and hemorrhagic stroke, 7 patients with TIA, and 2 patients with hemorrhagic stroke and TIA during the past one year. The number of the Cnm-expressing
S. mutans
carriers were 35 (15.2%). When divided by the median age, younger patients (<70 years) with stroke or TIA, compared to the older patients (≥70 years), had a higher carrier rate of Cnm-expressing
S. mutans
(22.7% vs. 8.3%,
p
< 0.001) and a lower prevalence of atrial fibrillation (6.4% vs. 22.5%,
p
= 0.001). Multivariate logistic regression analysis adjusted for sex, hypertension, and atrial fibrillation revealed that younger onset of stroke or TIA was independently associated with carriage of Cnm-positive
S. mutans
(adjusted odds ratio 1.26, 95% confidence interval 1.06–1.51;
p
= 0.009). Additionally, a tertile analysis based on age demonstrated the prevalence of Cnm-expressing
S. mutans
decreased as the age of stroke or TIA onset increased (24.6%, 12.5%, 9.9%;
p
for trend = 0.014).

Conclusion:
Oral carriage of Cnm-expressing
S. mutans
may confer a risk of earlier stroke or TIA. This finding suggests that targeting Cnm-positive
S. mutans
could be a promising novel therapeutic approach for preventing stroke or TIA.
Abstract WP317: Variations in the association between ECG Abnormalities and Stroke Subtypes: Findings from the INTERSTROKE Case-Control Study
Authors: McDermott Clodagh , Reddin Catriona , Costello Maria , Canavan Michelle , Smyth Andrew , Krewer Finn , O'Donnell Martin
Published: January 2025

Introduction:
Atrial fibrillation (AF), which can be easily identified through electrocardiogram (ECG), is a well-established predictor of ischemic stroke (IS) in comparison to other stroke subtypes. However, there is a paucity of literature surrounding other objective ECGs features and their discriminative abilities between stroke subtypes. This study explores the prevalence of ECG abnormalities and their potential associations with stroke and its subtypes.

Methods:
Our analysis included 10,363 IS cases, 3,055 hemorrhagic stroke (HS) cases, and 13,488 matched controls from the INTERSTROKE case-control study. The ECG abnormalities investigated included AF, recent ST-elevation myocardial infarction (STEMI), left ventricular hypertrophy (LVH), right ventricular hypertrophy (RVH), P-pulmonale, and P-mitrale. Multivariate logistic regression, and multinomial regression by stroke severity, was performed and adjusted for covariates. Analyses were conducted using R version 4.3.1.

Results:
In the population presenting with stroke, 19.26% exhibited ECG abnormalities (19.69% IS, 18.10% HS) compared to 7.1% of the controls. AF (7.4%) and LVH (11%) were the most reported abnormalities with recent STEMI, RVH, P-pulmonale and P-mitral each having a ≤1% prevalence (table 1). Regional variation was observed, with Africa having the highest detection of LVH (18%), and Western Europe/North America/Australasia having the highest detection of AF (9.2%).

Univariate and multivariate logistic regression analysis revealed AF as the strongest predictor of IS (OR 4.80, 95% CI 4.02–5.74), while LVH was the strongest predictor of HS (OR 5.35, 95% CI 4.06–7.04) (table 2). AF on presentation, significantly reduced the odds of a HS diagnosis (OR 0.22, 95% CI 0.14–0.33) compared to IS, while the converse was true of LVH (OR 1.76, 95% CI 1.35–2.29). Patients with LVH were significantly younger in age at stroke onset (61.0 ± 13.3 years vs. 62.3 ± 13.6 years, p < 0.001), particularly in the HS cohort (57.4 ± 12.8 years). LVH was most associated with severe stroke, defined as a modified Rankin score (mRS) of 4-6 on presentation (OR 1.20, 95% CI 1.03–1.41), compared to matched mild stroke cases.

Conclusion:
ECG abnormalities are commonly detected in patients presenting with stroke, and substantive differences between stroke subtypes was demonstrated. These findings suggest that ECG could play a critical role in rapid stroke differentiation and aid in the development of future clinical prediction tools.
Abstract WP326: The Association between Rheumatoid Arthritis and Stroke Risk by Serologic Status
Authors: Shin Alicia , Jung Jinhyung , Kim Hyungjin , Kang Seonyoung , Cho In Young , Kim Seyoon , Han Kyung-Do , Shin Dong Wook
Published: January 2025

Introduction:
Several previous studies showed increased risk in stroke in Rheumatoid Arthritis (RA) patients. However, no study has shown how risk differ among different serostatus of RA—seropositive RA (SPRA) and seronegative RA (SNRA) —and types of strokes —ischemic stroke (IS) and hemorrhagic stroke (HS).

Hypothesis:
We hypothesize that the incidence of stroke is higher in patients with RA compared to patients without RA, and there might be differences in risk by the serostatus of RA and usage of b/tsDMARDs.

Methods:
This nationwide cohort study used the South Korean National Health Insurance Service database, including participants over the age of 40, who were first diagnosed with RA between 2010-2017 with no previous stroke, and who had a health checkup within 2 years before the index date. A 1: 3 matched non-RA controls were established by age, sex, and index date. A total of 45,175 RA patients and 135,525 non-RA controls were included in the study. These participants were followed from 1 year after the index date to mitigate surveillance bias. For statistical analyses, Kaplan-Meier method and the multivariable Cox proportional regression analyses were conducted to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustment of income status, smoking status, level of physical activities, as well as comorbidities as covariates.

Results:
Patients with RA had a significantly higher risk for both ischemic (aHR 1.47, 95% CI 1.36-1.58) and hemorrhagic stroke (aHR 1.31, 95% CI 1.15-1.50) compared to controls. SPRA patients showed higher risk for both ischemic (aHR 1.56, 95% CI 1.43-1.69 for SPRA vs. aHR 1.23, 1.08-1.41 for SNRA) and hemorrhagic stroke (aHR 1.40, 95% CI 1.21-1.62 for SPRA vs. AHR 1.09, 95% CI 0.86-1.38 for SNRA). There seems to be no difference in stroke risk among RA patients between bDMARD user and non-user (aHR 1.41, 95% CI 1.13-1.51 for user vs. AHR 1.66, 95% CI 1.37-2.02 for non-user), but potential different was noted by the use of tsDMARD (aHR 1.43, 95% CI 1.34-1.53 for user vs. aHR 0.81, 95% CI 0.39 -1.70 for non-user) although not statistically significant.

Conclusion:
This study showed that patients with RA are at a significantly great risk for both ischemic and hemorrhagic stroke compared to those without RA, and that SPRA patients showed higher risk than SNRA patients. It also suggested potential protective effect of tsDMARDs in the prevention of stroke.
Abstract WP327: Identifying Novel Determinants of Death and Readmission Post-Stroke Using Explainable Machine Learning Algorithms
Authors: Veledar Emir , Zhou Lili , Gardener Hannah , Gutierrez Carolina , Brown Scott , Fakoori Farya , Johnson Karlon , Perue Gillian Gordon , Asdaghi Negar , Romano Jose , Rundek Tatjana
Published: January 2025

Background:
Identifying new determinants of death and hospital readmission can help inform target patient populations at high risk for poor transitions of care. Explainable machine learning (XML) algorithms are valuable tools to determine novel modifiable predictors in complex datasets. The goal of this study was to identify risk factors for death and readmission within 90 days post-stroke, focusing on novel non-clinical factors, including social determinants of health (SDOH), neighborhood characteristics, and post-stroke health behaviors. To achieve this goal, we explored the results of 11 distinct XML models, to identify predictors that were common and strong across models.

Methods:
The study population included 1300 stroke survivors in the Transitions of Care Stroke Disparities Study (TCSD-S), a prospective cohort of patients from 10 comprehensive stroke centers who participated in the Florida Stroke Registry in 2018-2023 (mean age=63.8 (13.9), 56% male, 22% Hispanic, 23% Non-Hispanic Black,51% Non-Hispanic White; 92% ischemic stroke). 90-Day death and readmission (N=192) were obtained from patient interviews and review of medical records. Data on 65 potential risk factors were obtained from Get With The Guidelines-Stroke (demographics, clinical characteristics, medical history, acute care), as well as publicly available neighborhood characteristics (SES, race/ethnicity, business density), and patient interviews at discharge (SES, living arrangement, social support) and 30 days post-stroke (health behaviors). We used 11 distinct XML models to identify the top 12 predictors of death or readmission in each model, resulting in 38 out of 65 distinct predictors across models. Predictors were ranked based on strength of association and consistency across models using feature agreement.

Results:
Table 1 shows model fit statistics across all XML models with best values in bold. Out of 38 identified predictors, 20 are non-clinical variables. Table 2 shows their rank order. The identified variables reflect the importance of SDH, environmental factors, and behavioral modifications, beyond traditional clinical predictors of death/readmission.

Conclusion:
XML methods emphasized the importance of non-clinical factors, including SDOH, environmental factors, and behavioral modifications, in transitions of stroke care and stroke outcomes. This illustration of the ability of XML models to find novel and nonobvious predictors may increase the trust in results produced by XML.
Abstract WP328: Higher Artificial Intelligence (AI)-ECG Atrial Fibrillation Prediction Model Output and Delta Age Computed from AI-ECG are Associated with Adverse Vascular Outcomes in Patients with Migraine
Authors: Chiang Chia-Chun , Chao Chieh-Ju , Yang Ping-Hao , Lopez-Jimenez Francisco , Mangold Kathryn , Attia Zachi , Friedman Paul , Noseworthy Peter , Zhang Nan
Published: January 2025

Migraine with aura(MwA) is associated with an increased risk of stroke and adverse vascular outcomes compared to those with migraine without aura (MwoA). AI-ECG prediction models developed at our institution can evaluate the probability of atrial fibrillation (AF) and estimate a patient’s age based on a normal sinus rhythm (NSR) ECG. Delta age, AI-ECG estimated age minus chronological age, indicates endothelial dysfunction and is associated with cardiovascular mortality. We aim to assess how AI-ECG prediction model outputs, specifically the AF probability and delta age, are associated with adverse vascular outcomes in patients with migraine.

Adult patients diagnosed with MwA and MwoA from 2000-2020 with at least one digital, standard 12-lead ECG were identified. The first ECG that showed NSR is used as the index ECG. Patients with any adverse vascular outcomes before the index ECG were excluded. Adverse vascular outcomes used as endpoints include acute ischemic stroke, acute myocardial infarction, deep vein thrombosis/pulmonary embolism, AF, and carotid artery dissection.

A total of 31301 patients (13783 MwA, 17518 MwoA) were included in our analysis. The mean age at the time of the index ECG was 44.3 (14.5), and the average follow-up time was 71.6 (69.8) months. Based on the index ECG, the mean AF probability was significantly higher in MwA compared to MwoA (2.39 vs 2.06, p< 0.001), while the delta age was lower in MwA compared to MwoA (3.7 vs 4.2, p <.001). The prevalences of all vascular outcomes are summarized in Table 1. Multivariate Cox regression models showed that a higher AF prediction model output (every 10% increase), as well as a higher delta age (every 10-year increase), are associated with an increased risk of composite vascular outcomes (HR1.20, 95%CI 1.17-1.23, p<.001, and HR1.19, 95%CI 1.14-1.23, p < .001) [Table 2]. The Kaplan-Meier curve of adverse vascular outcome-free survival by AF prediction model output, using 1% as the cutoff (HR 1.49, 95% CI 1.41, 1.57, p<.001), and by delta age, using 2-year as the cutoff (HR 1.14, 95% CI 1.08, 1.21, p <. 001) are presented in Figure 1. Having aura, older age, male, coronary artery disease, congestive heart failure, diabetes, hypertension, and tobacco use were also associated with a higher risk of adverse vascular outcomes.

Our results demonstrated the potential of using AI-ECG AF prediction model output and delta age to identify migraine patients at risk for adverse vascular outcomes.
Abstract WP331: Evaluating Disparities in Stroke Related to Mitral Valve Disorders in the United States (1999-2020) Using CDC WONDER Database
Authors: Naz Sidra , Lohana Sameer , Hotwani Priya , Adeem Mudassar , Naz Hira
Published: January 2025

Introduction:
Stroke is the second leading cause of death worldwide,around 50,000 U.S. residents with valvular heart disease experiencing a stroke annually. This study examines trends in stroke-related mortality due to mitral valve disorders (MVD) in the U.S. from 1999 to 2020, with a focus on demographic factors and racial disparities. The goal is to inform public health strategies and improve prevention and treatment efforts.

Methods:
We analyzed death certificate data from the CDC's WONDER database from 1999 to 2020, focusing on stroke and MVD-related mortality (ICD-10 code I64.0 “Stroke” and Code I34.0 “MVD”) in adults aged ≥25 years. Using joint point regression analysis, we calculated annual percent changes (APCs) in age-adjusted mortality rates (AAMRs) with 95% confidence intervals across various demographic (sex,race/ethnicity,age) subgroups.

Results:
The AAMR for stroke due to MVD-related mortality decreased in the US from an adjusted rate (AR) 98.6 in 1999 to 92.9 in 2001 (APC: -2.64%; 95% CI: -4.18% to -1.35%),after which it decreased to 59.6 in 2009 (APC: -5.47%; 95% CI: -6.20% to -5.19%) then it further reduced to 50.1 in 2015 (APC: -2.84%; 95% CI: -3.27% to -1.78%).The AAMR decreased in 2018 to 40.2 (APC: -7.28%; 95% CI: -8.08% to -6.22%) after which it increased to 43.9 in 2020 (APC: 4.15%; 95% CI: 2.56% to 5.59%). Males had higher consistently higher AAMRs than females (47.8 vs. 40.3).The AAMR in the US men decreased from 103.6 in 1999 to 51.5 in 2015 (APC: -2.62%; 95% CI: -3.04% to -1.49%) after which it decreased further to 42.2 in 2018 (APC: -6.75%; 95% CI: -7.72% to -5.48%)&then it increased to 47.8 in 2020 (APC: 6.11%; 95% CI: 4.10% to 7.85%).The AAMR in the US women decreased from 94.1 in 1999 to 48.3 in 2015 (APC: -3.05%; 95% CI: -3.51% to -1.75%) after which it decreased further to 38.2 in 2018 (APC: -7.57%; 95% CI: -8.81% to -6.18%) and then it increased to 40.3 in 2020 (APC: 2.32%; 95% CI: -0.26% to 4.49%).The non-Hispanic (NH) Black or African American (AA) has the greatest AAMR (69.2), followed by the NH American Indian or Alaska Native with an AAMR (44.2) and the NH White population with an AAMR (42.4).The low-risk populations were the Hispanic or Latino (33.6) and the NH Asian or Pacific Islander(31).

Conclusions:
The mortality rates from stroke due to MVD have overall increased in the United States over the past two decades, specifically men&(NH) Black or AA, NH American Indian or Alaska Native, and (NH) White are at high risk.
Abstract WP336: Elevated Trimethylamine N-Oxide Levels Are Associated with Ischemic Stroke and Hypertensive Intracerebral Hemorrhage
Authors: Nukata Ryotaro , tonomura shuichi , Yamamoto Akimasa , Iwamoto Soya , Chiba Tetsuya , Nakaoka Yoshikazu , Hattori Yorito , Ihara Masafumi
Published: January 2025

Background:
Trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite trimethylamine-containing nutrients, is mechanistically linked to atherosclerosis progression and platelet aggregation, leading to cardiovascular disease. Recent studies have showed that TMAO levels are elevated in patients with ischemic stroke; however, its association with heterogenous pathophysiology of stroke remains unknown. In this study, we aimed to investigate what stroke subtypes plasma TMAO levels were associated with.

Methods:
The study was prospectively conducted at a single center in Japan between 2021 and 2022, enrolling acute stroke patients and non-stroke subjects. Blood samples were collected at the first post-hospitalization or during a medical checkup after obtaining written informed consent. Plasma TMAO levels were measured using liquid chromatography-mass spectrometry. We compared TMAO levels between acute stroke patients and non-stroke subjects, as well as among stroke subtypes.

Results:
We enrolled 162 stroke patients (median age, 74) and 50 non-stroke subjects (75). Plasma TMAO levels were significantly higher in stroke patients than in non-stroke subjects (median [Interquartile range]: 3.0 [1.1–7.7] vs. 2.1 [0.8–4.2] µM,
p
= 0.01), and high TMAO levels (TMAO > 5.0 µM) distinguished stroke patients from non-stroke subjects (odds ratio 1.20, 95%CI 1.06-1.36,
p
< 0.01). High TMAO levels were independently associated with stroke after adjusted for age, sex, and conventional vascular risk factors (adjusted odds ratio 1.14, 95% confidence interval [CI] 1.01–1.28,
p
< 0.05). The proportion of patients with elevated TMAO levels was significantly higher in patients with cardioembolic stroke (11/34 [32%]), large-artery atherosclerosis (11/28 [39%]), small-vessel occlusion (11/36 [31%]), and hypertensive intracerebral hemorrhage (15/43 [35%]) than in non-stroke subjects (7/50 [14%]) (
p
< 0.05), but did not differ between patients with cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage (1/9 [11%]) and non-stroke subjects (
p
= 0.9).

Conclusions:
High plasma TMAO levels were significantly associated with hypertensive intracerebral hemorrhage as well as with each ischemic stroke type, but not with CAA-related intracerebral hemorrhage, suggesting that TMAO may confer a risk for stroke via the development of atherosclerosis.
Abstract WP338: Proteomic Analysis of Carotid Artery Plaques With and Without Vulnerable Features on Magnetic Resonance Angiography with Vessel Wall Imaging: A Pilot Study
Authors: Madden Benjamin , Polania-Sandoval Camilo , Pujari Ganesh , Mangalaparthi Kiran , Charlesworth Cristine , Prudencio Mercedes , Gendron Tani , Sandhu Sukhwinder , Nassar Aziza , Petrucelli Leonard , Meschia James , Pandey Akhilesh , Erben Young
Published: January 2025

Introduction:
Extracranial carotid artery pathology accounts for 15-20% of ischemic strokes. Advancements in magnetic resonance angiography (MRA) with vessel wall imaging (VWI) have enabled the identification of vulnerable plaques, aiding in risk stratification for neurovascular events. This pilot study aimed to identify proteins in plaques with and without vulnerable features on MRA with VWI.

Hypothesis:
There is a differential proteomic profile of vulnerable and non-vulnerable, thus, these can serve as potential biomarkers for disease progression, stroke prevention, and therapeutic targets.

Methods:
Consecutive patients undergoing carotid endarterectomy (CEA) were included in the study cohort with pre-operative MRA with VWI. A retrospective chart review was conducted to extract pertinent clinical data including cardiovascular risk factors and medications. The proteomic analysis involved Tandem Mass Tag (TMTpro) labeling of peptides, basic pH HPLC fractionation, and NanoLC-tandem mass spectrometry.

Results:
A total of sixteen plaques were retrieved from fifteen patients. There were 73.3% male patients. The most common comorbidities were hyperlipidemia (93.3%) and hypertension (80%). 31.2% of patients had symptomatic disease. Eleven plaques were vulnerable in preoperative MRI with VWI. From those, intraplaque hemorrhage was the most common feature (81.1%)
.
Proteomic analysis revealed 23 relevant proteins significantly elevated in vulnerable plaques, including Proteinase 3 (PRTN3), Phospholipid Transfer Protein (PLTP), and S100 Calcium-Binding Protein A12 (S100A12), with increased abundance exceeding two-fold changes or above (P<0.001). Conversely, three proteins exhibited reduced abundance in vulnerable plaques including Dynamin-3 (DNM3), Transmembrane Protein 181 (TMEM181), and Adducin-3 (ADD3) (P<0.05). All results are summarized in
Figure 1A-C and Table I and II.

Conclusion:
This study contributes to the understanding of protein biomarkers associated with carotid plaque vulnerability, offering insights into disease progression, stroke prevention, and identification of potential therapeutic targets
(Figure 1D)
. Furthermore, these patients could benefit from early surgical intervention if these biomarkers were to be detected. We present a comprehensive study of multiple proteins with significant bioavailability in explanted plaque specimens that can serve as a foundation for identifying blood biomarkers for future validation studies.
Abstract WP34: Targeted delivery of therapeutic genes into brain endothelial cells for treating brain AVMs.
Authors: Yadav Alka , Liang Rich , press kelly , Schmidt Annika , Shabani nabikandi Zahra , Leng Kun , Wang Calvin , Sekhar Abinav , Shi Joshua , Devlin Garth , Gonzalez Trevor , Asokan Aravind , Su Hua
Published: January 2025

Background and purpose:
Brain arteriovenous malformations (bAVMs) can cause life threatening intra-cranial hemorrhage. There is no effective drug therapy available to treat bAVM patients. Mutation of AVM causative genes in endothelial cells (ECs) induce bAVM development. Mutation of activin receptor-like kinase 1 (
Alk1
) or endoglin (ENG) causes a familiar form of bAVM. Transgene mediated Alk1 expression in ECs cured AVM phenotypes in mice with
Alk1
or Eng mutation. Adeno-associated viral vectors (AAVs) can be engineered to target different cells. We
hypothesize
that by screening engineered AAV vectors, an AAV variant can be identified that can transduce brain ECs specifically.

Methods:
A single-stranded CBA promoter driven tdTomato transgene was packaged into three engineered AAV capsids (AAV.cc47, AAV.cc84 and AAV1RX) and AAV9 (a vector that can penetrate the blood brain barrier). The vectors were delivered intravenously (i.v.) or intranasally (i.n.) to wild-type mice. A CMV promoter driven
Alk1
transgene was packaged into AAV.cc84 and delivered to PdgfbiCreER;
Alk1
f/f
mice through i.v. followed by induction of bAVM. Transduced cells in the brain and other organs, vessel density, pericytes, abnormal vessels in the bAVMs, and liver inflammation were analyzed histologically. Liver and kidney function were measured enzymatically. We also tested if AAV.cc84 can transduce human ECs by applying it to cultured HUVECs.

Results:
After i.v. delivery, AAV9 and AAV1RX transduced some brain cells. AAV9 also transduced some hepatocytes. AAV.cc47 did not transduce any brain cells but many hepatocytes. AAV.cc84 transduced many brain ECs and some hepatocytes. After i.n. delivery, AAV9 and AAV1RX transduced some brain cells, while AAV.cc84 predominantly transduced brain ECs. None of these vectors transduced hepatocytes. AAV.cc47 showed robust transduction in brain cells and hepatocytes. AAV.cc84-Alk1 restored Alk1 expression in about 50% of brain ECs of TM treated PdgfbiCreER;
Alk1
f/f
mice after i.v. injection, reduced vessel density and abnormal vessels, and increased vascular pericyte coverage. AAV.cc84 also transduced cultured HUVECs.

Conclusion:
The engineered AAV vector, AAV.cc84 can transduce brain ECs after i.v. and i.n. delivery effectively. AAV.cc84-Alk1 restored Alk1 expression in brain ECs and reduce bAVM severity in Alk1 deficient mice. Thus, this vector can be used for developing gene therapies to treat patients with HHT or sporadic bAVMs.
Abstract WP340: Red blood cells mediate the adverse effect of hyperglycemia on brain vasculature
Authors: Yin Shanye , McMullin David , Buonanno Ferdinando , Lo Eng , Ning MingMing , Deng Wenjun
Published: January 2025

Background:
Acute hyperglycemia is common post ischemic stroke, and is a robust predictor of poor stroke outcome. Even transient glucose elevation substantially increases the risk of mortality and long-term disability. Tight glucose control with insulin is effective in correcting hyperglycemia, but lacks efficacy in improving patient outcome, suggesting the presence of early hyperglycemic injuries that are resistant to later glucose control. Our recent clinical research revealed that abnormal red blood cells (RBCs) could be a novel mediator of the adverse effect of acute hyperglycemia on stroke outcome. Here, using in vitro and ex vivo models, we aim the explore the underlying mechanism.

Method:
RBCs were isolated from healthy C57BL6 mice (10~12 wk) and exposed to in vitro normal glucose (NG: 5 mM) or high glucose (HG: 15 mM) for 24 hr. HG-exposed RBCs were also treated with ROS scavenger TEMPOL (HG+TEMPOL). The treated RBCs were then incubated with mouse brain blood vessels for additional 24 hr. Changes in vascular gene expression were profiled via RNA sequencing.

Result:
HG exposure increased reactive oxygen species (ROS) production within RBCs, which was mitigated by TEMPOL (Figure 1A). Importantly, HG-challenged RBCs (HG-RBCs) led to a significant shift in brain vascular gene expression and function (Figure 1B-D). Specifically, the expression of endothelial nitric oxide synthase (eNOS), the enzyme responsible nitric oxide (NO) production, was decreased by HG-RBCs treatment, potentially reducing NO availability and compromising cerebral blood flow (Figure 2A). These changes were further validated by immunohistochemistry (Figure 2B, 2C). Moreover, RBCs affected vascular pathways linked to Alzheimer’s disease (Figure 1D). HG-RBCs suppressed Adam10 (α-secretase)-mediated non-amyloidogenic process and activated Bace1 (β-secretase)-mediated amyloidogenic process, potentially contributing to β-amyloid accumulation (Figure 2D, 2E). Most of these detrimental effects could be reversed by TEMPOL pretreatment (Figure 2A-E), and the overall vascular gene expression pattern was closer to those treated by NG-RBCs (Figure 1B, 1C), suggesting that hyperglycemia-induced RBC oxidative stress play a causal role in brain vascular dysfunction.

Conclusion:
RBCs, beyond their oxygen transport role, are crucial regulators of vascular function and could be a previously overlooked contributor to vascular dysfunction in acute hyperglycemia post stroke (Figure 3).
Abstract WP342: Inhibition of IL-6 Trans-Signaling Enhances Post-Stroke Functional Recovery: A Sex- and Dose-Dependent Study in mice
Authors: Nguyen Dustin , Hall Cassie , Chauhan Anjali
Published: January 2025

Background:
Elevated circulating IL-6 levels are associated with poor outcomes following stroke, and increased serum IL-6 levels correlate with worse stroke outcomes. IL-6 binds to soluble IL-6 receptors, binding to ubiquitously expressed gp130 to initiate proinflammatory trans-signaling. This exploratory study investigates the impact of inhibiting IL-6 trans-signaling on long-term functional outcomes in ischemic stroke.

Methods:
Young mice (8-15 weeks old) were administered recombinant saline/gp130Fc an IL-6 trans-signaling inhibitor, twice a week for two weeks, starting at the time of reperfusion after 60 minutes of post-middle cerebral artery occlusion (MCAO). Neurological deficit scores and infarct volumes were assessed at 24 hours, with long-term cognitive and motor evaluations conducted at 7 and 28 days post-MCAO. Gliosis and neurogenesis were analyzed via fluorescence microscopy, and plasma IL-6 levels were quantified using ELISA. Flow cytometry was performed to assess membrane IL-6 receptor and IL-6 levels on immune cells in the blood and brain at 24,72 hours and 7 days post-MCAO.

Results:
MCAO in young male mice significantly increased IL-6 expression while acutely reducing membrane IL-6 receptor levels in peripheral immune cells. Treatment with gp130Fc (0.5 mg/kg) effectively improved neurological deficit scores (NDS) and reduced infarct volume (p<0.05) at 24 hours post-stroke in male mice. This inhibition of IL-6 trans-signaling also mitigated cognitive decline and decreased tissue loss, inflammation, and SVZ IL-6 levels at sub-acute and chronic stages. In contrast, female mice did not improve cognitive function, tissue preservation, or neuroinflammation with the same treatment. Interestingly, female mice exhibited higher systemic IL-6 levels and elevated IL-6 expression on monocytes and neutrophils 24 hours post-stroke compared to age-matched sham controls. A higher dose of gp130Fc (1 mg/kg) was required to achieve significant neurological improvement and infarct reduction in female mice.

Conclusion:
These findings highlight the beneficial effects of inhibiting IL-6 trans-signaling with gp130Fc in both male and female mice. This demonstrates a clear dose-dependent response, with a higher dose needed for efficacy in females.
Abstract WP343: Effects of Exogenous Taurine Supplementation on Post-Stroke Recovery in Aged Mice
Authors: Couture Ben , Khan Romeesa , Quaicoe Victoria , Baskin Lynae , Devlin Patrick , Couture Lucy , Ritzel Rodney , Venna Venugopal
Published: January 2025

Background:
Taurine is a sulfur-containing amino acid present in most mammalian tissues that plays a critical role in regulation of numerous physiological processes. Taurine has been recently identified as a potential neuroprotective agent due to its potent antioxidant and anti-inflammatory properties. However, its effects on stroke recovery are unexplored. Here, we investigated the effects of chronic taurine supplementation on immune cells and recovery in aged stroke mice.

Hypothesis:
We hypothesized that aged stroke mice treated with taurine will show enhanced recovery compared to vehicle-treated mice. We examined if this beneficial effect was independent of infarct size and was associated with changes in immune cell responses.

Methods:
Human plasma samples were assessed by mass spectrometry in control and stroke patients. For murine studies, aged (16-18 months) C57BL/6 WT mice were subjected to a reversible 60-MCAO. Three days after stroke, mice were randomly assigned into two groups: one received taurine (n=6M,10F) and the other received water without taurine (n=5M,11F). Behavioral tests were performed at intervals until euthanasia on post-stroke day 42. Flow Cytometry (FACS) was performed to assess for cellular changes in the blood and tissues. Finally, as gut microbiota composition is implied in immune regulation, we determined changes in the microbiota following taurine treatment by performing 16s analysis on fecal samples.

Results:
First, we compared plasma taurine levels in healthy controls (n=20) and acute stroke patients (n=29) obtained through unbiased metabolomics. Taurine was significantly lower in stroke patients (p<0.05 by t test). We found plasma taurine levels decline after stroke in aged mice (p<0.05; n=6/grp). Post-stroke taurine supplementation in females resulted in significant regain of body weights (p<0.05). Mice received taurine had altered microbial composition and had a significant improvement in grip strength as early as 24 days after stroke (p<0.05), and improved neurological scores by day 18 in both males (p<0.05) and females (p<0.05) compared to controls. FACS data showed an increased number of B cells in the blood of taurine treated mice compared to controls (p<0.01).

Conclusion:
Our results show that stroke reduces taurine levels. Taurine significantly enhanced stroke recovery and led to immune cell changes in aged mice. These findings highlight a potential role of taurine as a therapeutic to enhance post-stroke recovery.