bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP17: Plasma Proteins In Correlation With Lesional Iron Content And Permeability Imaging In Clinical Trial Of Cavernous Angioma With Symptomatic Hemorrhage
Authors: Hage Stephanie , Bi Dehua , Li Ying , Srinath Abhinav , Debiasse Dorothy , Romanos Sharbel , Lightle Rhonda , Shenkar Robert , Lee Justine , Stadnik Agnieszka , Ji Yuan , Carroll Timothy J , Girard Romuald , Awad Issam A
Published: February 2023

Background:
Increases in mean lesional iron content (≥6%) measurement by QSM and vascular permeability (≥40%) assessed by DCEQP MRI have been associated with new bleeding, and are used as monitoring biomarkers in NINDS funded 1st clinical trial of pharmacotherapy (clinicaltrials.gov NCT02603328) in cavernous angiomas with symptomatic hemorrhage (CASH). Plasma protein levels previously associated with CASH in diagnostic and prognostic contexts have never been compared to lesional QSM and DCEQP in the same subjects.

Methods:
Plasma samples and MRI sequences were simultaneously acquired during 1 year-epochs of prospective follow-up of CASH patients. Plasma levels of 16 proteins were assayed by ELISA and correlated with lesional QSM and DCEQP during the same epochs. Univariate correlations were followed by multivariate analyses combining multiple protein levels to minimize Akaike Information Criterion (AIC) and increase R
2
. Accuracy (AUC on receiver operating curves) and sum of squared error (SSE) are reported for associations achieving statistical significance with FDR correction.

Results:
None of the proteins individually correlated with QSM/DCEQP (continuous or categorical). Relative change of angiopoietin2, and absolute change of the combination (endoglin+IL1B+IL16) had the highest accuracy (AUC 78.7%, SD 0.062 and 98.4%, SD 0.013 respectively) for lesional QSM increase ≥6%. Relative change of endoglin+IL1B, and absolute change of angiopoetin2+endoglin+thromobomodulin+VEGF, had the highest accuracy (AUC 64.6%, SD 0.057 and 93.2%, SD 0.040 respectively) for lesional DCEQP increase ≥40%. Relative change in angiopoetin1 had the lowest SSE (8.87) with QSM change as a continuous variable, and relative change in lipopolysaccharide binding protein had the lowest SSE (469.06) with DCEQP change as continuous variable.

Conclusion:
Circulating proteins reflect changes in lesional iron content and permeability in CASH during prospective follow-up. Results are a proof of concept that blood tests could replace more complex and costly imaging biomarkers in the monitoring of hemorrhage in cavernous angiomas. Additional mechanistic plasma molecules (miRNAs and metabolites) may further enhance the accuracy of these monitoring biomarkers.
Abstract WP174: Elevated Homocysteine Intensify The Effect Of Lipoprotein(a) On Stroke Recurrence
Authors: Feng Zhiyuan , Xu Jie , Wang Yongjun
Published: February 2023

Introduction:
Lipoprotein(a) [Lp(a)] and homocysteine (tHcy) are risk factors for ischemic stroke. tHcy show great impact on Lp(a) binding to fibrin and interaction between Lp(a) and Mac-1 integrin, which might intensify the atherogenic and thrombotic pathway mediated by Lp(a). The study aims to explore the effect of Lp(a) on stroke recurrence within 1 year in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA), based on different tHcy level.

Method:
A total of 10068 patients with AIS or TIA from the third China National Stroke Registry cohort were included. Since Lp(a) levels vary strongly between ethnicities, the cut-off value was set at the 80
th
percentile based on National Lipid Association recommendation. The association between Lp(a) and stroke recurrence was evaluated using Cox proportional hazards model. Patients were further categorized to five different subtypes according to the TOAST criteria. The interaction between Lp(a) and tHcy was tested in different subtypes.

Result:
8054 patients were classified into the ≤80
th
group, 2014 patients were classified into the >80
th
group. No significant differences were found between the two groups in terms of age, sex, and traditional risk factors (P>0.05). 999 patients experienced recurrent stroke in 1 year follow-up. Patients with Lp(a)>80
th
patients had a higher risk of stroke recurrence (11.57% vs 9.51%). Patients were further stratified by tHcy (>15 and ≤15 μmol/L). Among all patients, the highest recurrence rate (12.8%) was observed in the patients with elevated both Lp(a) and tHcy (aHR 1.41; 95%CI 1.14-1.74), the interaction between Lp(a) and tHcy was observed (P=0.03). We also found significant interaction among large-artery atherosclerosis (LAA) subtype (P<0.01).

Conclusion:
The finding indicated elevated tHcy might intensify Lp(a)-associated stroke recurrence. Elevated Lp(a) should receive more attention in AIS/TIA patients with elevated tHcy, especially in the LAA subtype.
Abstract WP18: Association Of Quality Of Life Domains And Clinical Symptoms In Familial Cerebral Cavernous Malformation Patients
Authors: Tsang Cynthia , Nelson Jeffrey , McCulloch Charles , Smith Edward R , Vadivelu Sudhakar , Akers Amy , Lee Cornelia , Zabramski Jospeh , Zafar Atif , Torbey Michel T , Morrison Leslie , Awad Issam A , Kim Helen
Published: February 2023

Background:
Familial cerebral cavernous malformation (FCCM) is characterized by multiple brain lesions at risk for intracranial hemorrhage (ICH) and neurological morbidity, affecting quality of life (QoL). PROMIS-29 is a QoL survey validated in some neurological diseases but has not yet been evaluated for FCCM. We aimed to assess whether PROMIS-29 health domains are associated with clinical symptoms in FCCM patients.

Methods:
PROMIS-29 surveys assessing seven QoL domains were completed by 198 FCCM patients >=18 years either at a baseline or follow-up visit in the Brain Vascular Malformation Consortium CCM study. Raw PROMIS-29 domain scores were converted to T scores that are standardized to a reference population with mean 50 and SD 10, and oriented so that higher scores are unfavorable. One-sample t-tests and p-values assessed whether mean T-scores were significantly different from 50 (p<0.05). Multivariable linear regression was used to test whether domain scores were associated with history of ICH, seizures, or headaches at time of survey, adjusting for age and sex.

Results:
Compared to a reference population, FCCM patients had significantly higher anxiety (52.7, 95% CI: 51.3-54.2, p<0.001), pain (52.5, 95% CI: 51.0-54.0, p=0.002), and physical functioning scores (52.0, 95% CI: 51.4-54.5, p<0.001), but lower social participation scores (46.9, 95% CI: 45.4-48.5, p<0.001). History of ICH and headaches were significantly associated with 4 domains each (all >3 points, p<0.05, Table), while seizures were not associated. Fatigue was the only affected domain in common.

Conclusion:
FCCM patients differed significantly from the reference population on anxiety, pain, physical functioning, and social participation domains. These same domains were significantly associated with history of ICH or headaches in patients. Further studies will determine whether changes in health domains are associated with changes in clinical symptoms.
Abstract WP183: Social Activities Are Positively Associated With Medication Adherence In Stroke Survivors
Authors: Ding Xueting , Wing Jeffrey J , Gibbs Brooke H , Drum Emily , Gutierrez Desiree , Albala Bruce , Boden-Albala Bernadette
Published: February 2023

Introduction:
Social support may influence illness incidence or recovery through effects on health-related behaviors, and one aspect is emotional support, which includes the offering of empathy, friendship, care, and trust along with information. While we have previously reported on the positive relationship of family and friend networks in risk reduction, our objective was to examine whether participation in formalized group activities was related to medication adherence post-stroke.

Methods:
Using Discharge Educational Strategies for Reduction of Vascular Events (DESERVE) data, information regarding religious and nonreligious social activities was collected at baseline. The outcome variable was measured by the self-reported 8-item Morisky Medication Adherence Scale (MMAS-8; score 0-8). Medium/high adherence (MMAS-8≥6) at 6- and 12-months post-discharge was modeled against social activities separately using logistic regression adjusting for age, gender, race/ethnicity, education, family and friend networks, NIH stroke scale at admission, and the intervention.

Results:
Of the 541 participants who completed the baseline questionnaire, 286 and 344 had valid MMAS-8 scores for post 6-months and 12-months follow-up data collection. Medication adherence was poor among the participants. Only 44% for 6-months and 46% for 12-months had medium or high medication adherence. Participants going to nonreligious social events (n = 67, 21%) had higher odds of having medium/high medication adherence (OR = 3.08, 95% CI: 1.15-8.25) at 12-months.

Discussion:
Nonreligious social activities, including meetings of social clubs or other non-religious groups not relevant to work, were shown to be positively related to 12-months post-discharge medication adherence among stroke patients. Social activities may play an important role in emotional support and may be an opportunity for targeted secondary stroke prevention.
Abstract WP185: Relationship Between E-cigarette Smoking And Stroke - A NHANES Study
Authors: Patel Neel , Patel Urvish K , Mehta Neev , Urhoghide Eseosa , Patel Nidhi , Patel Amrapali , Parulekar Akshada , Fernando ortiz Juan , Patel Rutul , Mistry Anuja , Bhriguvanshi Arpita , Khurana Mahika , Abdulqader Mohammed , Arumaithurai Kogulavadanan , Shah Shamik
Published: February 2023

Introduction:
Tobacco use is a known risk factor for stroke and other cardiovascular diseases. However, the relationship between e-cigarette smoking and stroke is largely unknown.

Hypothesis:
This study aims to assess the effect of e-cigarettes among people who have had a history of stroke.

Methods:
A cross-sectional survey was performed using the NHANES database from 2015 to 2018 in the US population. We identified participants 18 or older with a history of stroke and their smoking habits (e-cigarette, traditional, and dual smoking). The chi-square test, unpaired t-test, and multivariable logistic regression models were used to examine the association of e-cigarette consumption among the stroke population.

Results:
Out of a total of 266,058 respondents, 79,825 were smokers [E-cigarette: 7,756 (9.72%); Traditional: 48,625(60.91%), Dual smokers: 23,444 (29.37%)] Overall prevalence of stroke was 5.41% (n=4194) amongst various types of smokers. Amongst females with stroke, the prevalence of e-cigarette use was higher compared to traditional smoking. (36.36% vs 33.91%; p<0.001) Mexican Americans (21.21% vs. 6.02%) and other Hispanics (24.24% vs. 7.70%) had a higher prevalence of e-cigarette use than traditional smoking. (p<0.001) E-cigarette smokers were having an early onset of stroke in comparison with dual and traditional smokers. (Median age in years: 48 vs. 50 vs. 59, respectively; p<0.001). Stroke was more prevalent amongst traditional smokers compared to e-cigarette and dual smokers (6.75% vs. 1.09% vs. 3.72% p<0.001). In multivariable logistic regression analysis, the odds of having a history of stroke were higher amongst e-cigarettes in comparison with traditional smokers. (aOR:1.15; 95%CI: 1.15-1.16; p<0.001).

Conclusion:
Although stroke was more prevalent in traditional smokers, e-cigarette smokers had early-onset and higher odds of stroke compared to traditional smokers. More prospective studies are needed to evaluate the long-term effects and safety of e-cigarettes to mitigate the risk of cardio and cerebrovascular disorders.
Abstract WP187: Takotsubo Cardiomyopathy And Subsequent Risk Of Major Adverse Cardiovascular Events: A Cluster Analysis
Authors: Alvarado-Bolanos Alonso , Fridman Sebastian , Ayan Diana , Sposato Luciano A
Published: February 2023

Introduction:
Takotsubo Cardiomyopathy (TCM) is a form of transient regional left ventricular dysfunction. The risk of MACE after TCM is poorly understood but appears to be higher. Predictors of cardiovascular (CV) events remain unclear.

Methods:
Retrospective study of patients admitted to London Health Sciences Centre hospitals with TCM between 2014 and 2021. Clinical data were collected. MACE during follow-up (FU) included stroke, acute coronary syndrome, admission for heart failure or CV death. Outcomes were assessed until the end of FU. A two-step cluster analysis was used to stratify patients' phenotypes. Variables for clustering included: TCM aetiology, age, sex, hypertension, dyslipidemia, smoking, previous stroke, diabetes, chronic kidney disease, ejection fraction, atrial fibrillation (AF), and antithrombotics. A Cox proportional-hazards model was used to determine the association between clusters and MACE.

Results:
We included 152 patients (88.8% females). Median age was 72.5 [65.5-80.0] years and aetiologies were emotional stress (31.6%), neurogenic (6.6%), acute medical conditions (23.7%), and unknown (38.2%). Overall, 80% received antithrombotic drugs post-TCM. At a median FU of 22.0 [8.2-44.5] months, 11.8% of the patients experienced a MACE. Cluster 1 (n=41) included more male patients (31.7%), and the highest rate of hypertension (100%), dyslipidemia (92.7%), smoking (31.7%), previous stroke (14.6%), and antiplatelet use (82.9%). Cluster 2 (n=21) included older patients (78 [73.5-84.5] years) with the highest prevalence of diabetes (23.8%), AF (95.2%) and anticoagulation (71.4%). Cluster 3 (n=90) included younger patients (69 [62.7-84.0] years) with the lowest burden of CV risk factors (CHA
2
DS
2
VASc 2.0 [1.0-2.2]) and antithrombotic therapy (68.9%). Cluster 1 was associated with increased risk of MACE (OR 2.9; 95%CI 1.1-7.3; p=0.02) and stroke (OR 4.9; 95%CI 1.1-20.6; p=0.02).

Conclusion:
CV events are relatively frequent after a diagnosis of TCM, affecting over one-tenth of patients. We identified a high-risk phenotype, predominantly characterized by male sex, a higher burden of CV comorbidities, and low anticoagulation rates, which was associated with an increased risk of MACE and stroke after TCM.
Abstract WP188: Relationships Of Hematocrit With Asymptomatic And Symptomatic Lacunar Ischemic Lesions
Authors: Roh David , Murguia Fuentes Ricardo , Gurel Kursat , Khasiyev Farid , Rahman Salwa , Bueno Pedro , Kozzi Khrystyna , Spagnolo-Allende Antonio , Cottarelli Azzurra , Simonetto Marialaura , Ji Robin , Guo Jia , Spektor Vadim , Hod Eldad , Burke Devin , Konofagou Elisa , Rundek Tatjana , Wright Clinton , Marshall Randolph S , Sacco Ralph L , Elkind Mitchell , Gutierrez Jose
Published: February 2023

Introduction:
Hematocrit at both low and high extremes can result in both hypoxia and thrombosis respectively. While both scenarios may predispose to ischemia, it is unclear whether hematocrit associates with small vessel cerebrovascular lacunar infarcts.

Hypothesis:
Hematocrit levels will associate with both asymptomatic and symptomatic cerebrovascular lacunar infarcts in stroke-free participants and ischemic stroke patients, respectively.

Methods:
A cross sectional observational analysis of a prospective, population-based cohort study of stroke-free, older adult (>50) participants from the Northern Manhattan study (NOMAS) receiving baseline hematocrit testing and MRI between 2003-2008 were analyzed. A second, single center prospective cohort of admitted adult ischemic stroke patients receiving baseline hematocrit testing and MRI between 2005-2018 was evaluated. Associations of hematocrit with covert, asymptomatic chronic lacunar infarcts from stroke-free participants in NOMAS were assessed using general additive models after adjusting for relevant covariates. Separate analyses were performed to assess associations of hematocrit with symptomatic acute lacunar infarct stroke etiology using similar adjusted models for patients admitted and enrolled into the ischemic stroke registry.

Results:
Of 1218 NOMAS participants analyzed, 6% had covert chronic lacunar infarcts. The association between hematocrit and covert chronic lacunar infarcts was U-shaped (X2: 9.21; p-value: 0.03). In the 1489 patients from the ischemic stroke registry, 23% were identified to have symptomatic acute lacunar infarcts. Linear relationships were identified with higher hematocrit and symptomatic acute lacunar infarct etiology (adjusted coefficient beta: 0.020; standard error: 0.009; p=0.03).

Conclusions:
We identified relationships of hematocrit with both asymptomatic and symptomatic lacunar infarcts in both stroke-free and ischemic stroke cohorts, respectively. There may be a relevant role of red blood cell volumes with ischemic cerebral small vessel disease pathophysiology. However, further studies are required to clarify the mechanisms behind these relationships.
Abstract WP189: Association Between Neighborhood Socioeconomic Characteristics, Cardiovascular Health, And Incidence Of Stroke
Authors: Palakshappa Deepak , Davis Armstrong Nicole D , Tanner Rikki M , Keene Keith L , Hsu Fang-Chi , Irvin Marguerite M , Aldridge Chad M , Sunmonu N A , Worrall Bradford
Published: February 2023

Introduction:
Social and environment factors are associated with increased stroke risk. It is unclear if favorable cardiovascular health may attenuate this risk. We evaluated the impact of neighborhood socioeconomic characteristics on stroke incidence, and if levels of cardiovascular health modify this relationship.

Methods:
We conducted a longitudinal cohort study of Black and White participants using data from the Reasons for Geographic and Racial Differences in Stroke. We included all stroke-free participants and geocoded their home addresses to the census-tract level. Our primary exposure was neighborhood socioeconomic condition index (nSES; in quartiles) constructed using data from the U.S. Census on income, education, and occupation of residents by census tract. We evaluated cardiovascular health based on the American Heart Association’s Life Simple 7 (ideal, adequate, inadequate). We used a Cox proportional hazards model to regress nSES and its interaction with Life Simple 7 on stroke incidence, adjusting for individual demographics, socioeconomic status, and clinical characteristics.

Results:
We included 26,941 adults with a mean follow-up of 11.6 years (SD ± 5.2). During the study, 1,596 (5.9%) participants had a first incidence of stroke. Participants within the lowest nSES quartile, compared to those in the highest, were more likely to be Black, have lower household income, and an inadequate Life Simple 7 score. In multivariable models, there was a non-significant increased incidence of stroke (HR-1.13; 95% CI: 0.95-1.35) between the lowest and highest nSES quartiles. The interaction between nSES and Life Simple 7 was also non-significant for stroke incidence with worse cardiovascular health across all quartiles.

Discussion:
Among a national cohort of Black and White adults, we found a non-significant difference in stroke incidence between adults who live in worse neighborhood socioeconomic conditions and have inadequate cardiovascular health. Characterizing the potential contribution of social, environmental, and health behaviors could inform clinical and public health strategies to mitigate stroke risk.
Abstract WP190: Central Retinal Artery Occlusion: Do Patient Presentation Patterns Complicate Use Of Potential Treatments?
Authors: Shah Ronak , Gilbert Aubrey , Melles Ronald , Patel Amar , Do Timothy , Wolek Michael , Vora Robin
Published: February 2023

Introduction:
For patients diagnosed with central retinal artery occlusion (CRAO), timely screening for underlying risk factors to prevent secondary stroke and other cardiovascular events is required. Given the profound impact on vision, there is also great interest in the potential to treat CRAO. Thrombolytic therapy is the current standard of care in acute ischemic cerebral stroke, but the window for administration is short. As part of a larger pilot to investigate the prospect of intravenous thrombolysis for patients presenting with acute CRAO in our institution, we set out to evaluate the specific presentation patterns of this population within our system.

Methods:
Retrospective study performed on 804 patients correctly diagnosed with CRAO from 2011-2020. From this cohort of patients, we identified 484 for whom we could accurately determine the time of first symptoms, the time of first contact with the healthcare system, and the time of evaluation by an ophthalmologist.

Results:
While 18.0% (87/484) of patients waited over 24 hours from time of vision loss to contact the health care system, 50.2% of patients did connect in under 4.5 hours (243/484). However, only 16.7% (81/484) of patients saw an ophthalmologist within that window, and 35.5% (172/484) did not have any ophthalmologic evaluation within 24 hours of vision loss.

Conclusion:
Half of CRAO patients within our institution connect with the health care system within a potential window for intravenous thrombolytic treatment, but the majority do not receive ophthalmic diagnosis within that time frame. In conclusion, public health education efforts to speed up presentation times and system-based strategies to decrease the time to ophthalmic diagnosis are needed if thrombolytic treatment either via compassionate use or within a clinical trial setting is to be more widely offered.
Abstract WP194: The Prevalence Of Intracranial Artery Stenosis And Ischemic Stroke In Familial Hypercholesterolemia: A Retrospective Cohort Study
Authors: Noda Kotaro , Hattori Yorito , Hori Mika , Tanaka Akito , Nagai Atsushi , Harada-Shiba Mariko , Yamaguchi Shuhei , Ihara Masafumi
Published: February 2023

Introduction:
Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder, characterized by the early-onset elevation of LDL cholesterol (LDL-C) levels and premature coronary artery disease (CAD). Although the association between FH and CAD is well known, that between FH and cerebrovascular diseases including stroke and intracranial artery stenosis (ICAS) is still unclear. We hypothesized that long-standing excessive LDL-C levels in FH patients confer an increased risk of developing ICAS, and consequently FH patients are subject to ischemic stroke (IS). The aim of our study is to unveil the relationship between FH and cerebrovascular diseases including ICAS and IS.

Methods:
The associations of FH and high LDL-C with IS and ICAS were tested in neurologically normal subjects (NNS) who voluntarily underwent brain MRI from December 2000 to September 2011 at Health Science Center in Shimane, Japan, and FH patients who underwent brain MRI at National Cerebral and Cardiovascular Center in Japan from May 2005 to March 2020. The severity of ICAS was evaluated with MRA.

Results:
We enrolled 3181 NNS and 167 FH patients with the mean age of 62.3±0.2 and 61.5±1.3, respectively (
p
= 0.10). There were 1159 females (46.2%) in NNS and 89 (53.3%) in FH patients (
p
= 0.075). The prevalence of ICAS in the FH patients was significantly higher than in the NNS (5.7% vs. 37.1%,
p
< 0.001), and the incidence of IS was also higher in the FH patients (0.8% vs. 10.8%, p<0.001). Multiple regression analysis revealed that FH was an independent predictor for IS (OR 13.96, 95%CI 6.60-29.55,
p
< 0.001). Kaplan-Meier analysis showed a significant difference in the incidence of IS between the NNS and FH patients (
p
< 0.001). Moreover, the presence of ICAS significantly associated with the incidence of IS in the FH patients (Cox regression analysis: HR 6.55, 95%CI 1.66-25.78,
p
= 0.007).

Discussion:
Our study demonstrated a significantly higher prevalence of ICAS in FH patients than control subjects with similar age. Moreover, ICAS conferred an increased risk of IS among the FH patients. These results may necessitate routine examinations of the brain as well as systemic arteries in FH patients. We conclude a positive relationship of FH with cerebrovascular diseases, including ICAS and IS.
Abstract WP196: Seasonal Variation In Stroke Ischemic Hospitalization: Results From The A Large Health System In Six Western States Of The United States.
Authors: Bavarsad Shahripour Reza , Azarpazhooh Datis , Maleki Ana , osouli Sima , Baraban Elizabeth , Marginean Horia , Arnold Lisa , Tarpley Jason W
Published: February 2023

Background:
Evidence of seasonal variations in the incidence of stroke is inconsistent with some studies reporting no association and some a significant rise in different months of the year. In addition, less is known about how seasonality impacts the incidence of stroke subtype.

Methods:
This was a cross-sectional, observational study of data from a multi-state health system’s stroke registry (n=40 hospitals) in Alaska, California, Montana, Oregon, Texas, and Washington state. We included all cases with acute ischemic stroke admitted from September 29, 2016, to November 30, 2021. Admission data were categorized according to four meteorological seasons: winter, spring, summer, and fall. Acute ischemic stroke was categorized into two sub-types as large vessel occlusion (LVO) or non-LVO. We calculated the aggregate number of individuals admitted with stroke by season. Using, linear regression models with generalized estimating equations (GEE), we assessed the relationship between meteorological season and daily hospitalization rate. We used R version 4.0.4 (2021-02-15) for both the descriptive and inferential analyses and the R gee pack package (version 1.2-1) to perform GEEs.

Results:
During the study period, we identified 18,886 patients with acute ischemic stroke (median age: 73; 49.5% women). Acute ischemic stroke was more commonly observed during winter compared with other seasons with some variations between the selected regions. Based on a generalized estimating equations model, stroke hospitalization increased during winter, with an additional 3.3 cases per day (95%, CI [2.4, 4.1]). Winter is also associated with a higher incidence of large vessel occlusion.

Conclusion:
The incidence of ischemic stroke, including cases of large vessel occlusion, increased during the winter months. The results are important for human resource allocation for better management of cases with ischemic strokes.
Abstract WP197: The Association Between Atherosclerotic Disease And Cervical Artery Dissection In A Large Population-based Cohort Of Older People
Authors: Kahan Joshua , Zhang Cenai , Liberman Ava L , Segal Alan Z , Murthy Santosh , Kamel Hooman , Merkler Alexander E
Published: February 2023

Introduction:
While well-established risk factors for cervical artery dissection include trauma and connective tissue disorders, many cases are considered “spontaneous.” Although the incidence of cervical artery dissection is greatest in the young, the prevalence increases with age, suggesting a potential role of vascular disease. In this study, we hypothesized that atherosclerosis may be a risk factor for cervical artery dissection.

Methods:
We performed a retrospective cohort study using administrative claims data from a 5% sample of Medicare beneficiaries between 2008 and 2018. The exposures of interest were vascular risk factors potentially associated with atherosclerosis including coronary artery disease, hyperlipidemia, hypertension, diabetes mellitus, heart failure, chronic kidney disease, chronic obstructive pulmonary disease, valvular heart disease, atrial fibrillation, tobacco use, and alcohol abuse. The primary outcome was a new diagnosis of cervical artery dissection. Marginal structural Cox models were used to characterize the association between the exposures and outcomes, adjusted for time-dependent confounding, age, sex, race/ethnicity, and prior stroke.

Results:
Among 2,256,826 eligible Medicare beneficiaries, 1,527 (0.07%) developed cervical artery dissection, with a mean age of 70.8, compared to 71.5 in those without cervical artery dissection. The following exposures were found to be significantly associated with the development of cervical artery dissection: coronary artery disease (1.81 [1.63-2.01]), hyperlipidemia (1.84 [1.61-2.11]), hypertension (2.04 [1.76-2.37]), diabetes mellitus (1.34 [1.21-1.49]), heart failure (1.44 [1.25-1.67]), chronic kidney disease (1.38 [1.20-1.59]), chronic obstructive pulmonary disease (1.3 [1.16-1.46]), valvular heart disease (1.81 [1.60-2.04]), atrial fibrillation (HR 1.75 [95% CI 1.54-1.98]), tobacco use (1.84 [1.57-2.15]), and alcohol abuse (1.84 [1.56-2.16]).

Conclusion:
In a large population-based cohort of older people, atherosclerotic risk factors were associated with subsequent cervical artery dissection. Further studies exploring the role of atherosclerosis in the development of cervical artery dissection are required.
Abstract WP198: Microatherosclerosis Is A Common But Often Overlooked Cause Of Ischemic Stroke
Authors: Hidalgo Rafael L , Saver Jeffrey L
Published: February 2023

Background:
Clinicians frequently ascribe lacunar strokes to lipohyalinosis/arteriosclerosis, but classic neurovascular pathology studies lacunar infarcts are more often due to “microatherosclerosis” (small atheromatous plaque within penetrating arteries). The proportion of lacunar infarcts in clinical practice due to microatherosclerosis has not been previously quantified.

Methods:
The findings in all reported neuropathologic studies were catalogued for the 4 lacunar syndromes of pure motor hemiparesis (PMH), pure sensory stroke (PSS), dysarthria-clumsy hand (DCH), and ataxic hemiparesis (AH). Systematic meta-analyses, per PRISMA guidelines, were performed of large clinical series of consecutive ischemic stroke patients to delineate: 1) the proportion of all ischemic strokes due to lacunar infarcts, and 2) among the lacunar events, the relative frequencies of PMH, PSS, DCH, and AH.

Results:
Neuropathology showed: PMH caused by microatherosclerosis in 64%, parent artery ostial atherosclerosis in 7%, lipohyalinosis in 14%, and embolism in 14%; PSS caused by lipohyalinosis in 100%; DCH caused by embolism in 100%; and AH caused by microatherosclerosis in 100%. In the systematic review, among 22 large ischemic stroke series enrolling 25,260 patients, frequency of lacunar infarct was 18.8% (±5.1%). Among 5 large series enrolling 838 lacunar infarct patients, subtype frequencies were: PMH 45.5%, PSS 17.7%, DCH 7.4%, and AH 2.9% (with the remainder sensorimotor stroke and less common lacunar syndromes). Quantitative synthesis indicated that, among lacunar strokes, microatherosclerosis is the most common cause (44%), followed by lipohyalinosis (33%), and parent artery athero or embolism (combined 23%). Among all ischemic strokes, microatherosclerosis is the cause in 6%.

Conclusion:
Microatherosclerotic plaque within a penetrating artery is a common cause of cerebral ischemia, accounting for 6% of all ischemic strokes. This substantial burden of microatherosclerosis is the likely pathophysiologic basis for the benefits of thrombolytic and statin therapy in lacunar ischemic stroke.
Abstract WP199: Moderately Reduced Left Ventricular Ejection Fraction Is Associated With Embolic Stroke Of Undetermined Source And Lower Odds Of Atrial Fibrillation Detection
Authors: Goldstein Eric , Shu Liqi , Chen Edward , Bashir Zubair S , Wang Shuyuan , Rana Maheen , Kala Narendra , Dai Xing , Mandel Daniel , Has Phinnara , Simmons James , Song Christopher , Haines Philip , Yaghi Shadi
Published: February 2023

Introduction:
Embolic stroke of undetermined source (ESUS) is suspected to be primarily of cardioembolic origin with ongoing trials evaluating cardiac biomarkers to confirm or refute this theory. Presently, it is unclear whether left ventricular ejection fraction (LVEF) is a contributor to ESUS and whether LVEF influences identification of atrial fibrillation (AF) on mobile telemetry. We hypothesized that lower LVEF is associated with the ESUS stroke subtype and higher likelihood of capturing AF.

Methods:
We retrospectively obtained data through the Comprehensive Stroke Program at Rhode Island Hospital. Those included were adults diagnosed with ESUS on discharge defined as an emboliform ischemic infarct, LVEF >30%, no ipsilateral stenoses > 50%, and cardiac telemetry for at least two weeks without contributory dysrhythmia. Data was compared with a non-cardioembolic (NCE) ischemic stroke population. A transthoracic echocardiogram was performed while hospitalized and interpreted by a cardiologist. A subset of those with ESUS completed cardiac monitoring whose data was retrospectively reviewed. LVEF was categorized as 30 - 54%, 55 - 65%, and > 65%. Standard descriptive and logistic regression analyses adjusted for age were used for statistical interpretation.

Results:
We identified 677 participants (ESUS: 324, NCE: 353); mean age was 66 years and 55% were male. In adjusted models, there was an association between ESUS subtype and LVEF 30 - 54% (vs. LVEF >65%) OR 2.51, 95%CI 1.27 - 4.95, p = 0.008 and LVEF 55 - 65% (vs. LVEF > 65%) OR 1.38, 95%CI 0.97 - 1.97, p = 0.077. With LVEF treated as a continuous variable, every 5% increase in LVEF lowered the likelihood of an ESUS subtype diagnosis (OR 0.85 95% CI 0.76-0.94 p=0.002). Those with a LVEF of 30 - 54% or LVEF > 65% had a lower rate of AF detection than patients with LVEF 55 - 65% (OR 0.37, 95%CI 0.16 - 0.85, p = 0.019) on prolonged monitoring.

Conclusions:
ESUS subtype was more common with lower LVEF. AF detection was lower amongst the lowest and highest LVEF ESUS subtype groups. This suggests that both LVEF and AF separately contribute to ESUS. Studies are needed to confirm our findings and improve stroke prevention strategies in patients with low LVEF and ESUS.
Abstract WP200: Susceptivity Vessel Sign In Cardioembolism Due To Atrial Fibrillation: Association Between Blood Viscosity And Dihomo-γ-linolenic Acid
Authors: Okumura Motohiro , Sato Takeo , Kokubu Tatsushi , Takahashi Junichiro , Kitagawa Tomomichi , Nakada Ryoji , MAKI TANABE , ONDA ASAKO , Komatsu Teppei , Sakuta Kenichi , Sakai Kenichiro , Umehara Tadashi , Mitsumura Hidetaka , Iguchi Yasuyuki
Published: February 2023

Background and Purpose:
Blood viscosity (BV) is associated with blood stagnation leading to thrombosis. Some polyunsaturated fatty acids (PUFAs) are said to have an antithrombotic effect. First, we aimed to determine the association between BV and the presence of the susceptivity vessel sign (SVS) in patients with cardioembolism (CE) due to atrial fibrillation (AF). Second, we aimed to reveal the association between BV and PUFAs levels.

Methods:
Consecutive patients with ischemic stroke who met the following inclusion criteria were included: 1) patients with CE, defined by TOAST classification, secondary to AF; 2) onset to door time within 24 h; 3) availability of MRI, including susceptibility-weighted images, obtained at our hospital before IV rt-PA and/or MT; and 4) availability of PUFAs measurements on the day of or the day after the hospital visit. Hematocrit-derived BV at high shear rate (300 sec
-1
) was calculated using the following formula: BV = 1.4175+ 5.878*Ht - 12.98*Ht
2
+ 31.964*Ht
3
(Ht = Hematocrit/100). First, we assessed whether BV could be associated with the presence of SVS. Second, we evaluated whether some PUFAs (dihomo-γ-linolenic acid [DGLA], arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid) levels could be the factors associated with BV.

Results:
We screened 1,720 consecutive ischemic stroke patients and included 137 patients (95 [69%] male, median age 73 years). Of 137, SVS was observed in 83 (61%) patients. In multivariable logistic regression analysis, BV was independently associated with the presence of SVS (odds ratio [OR] 0.391, 95% confidence interval [CI] 0.18-0.86,
p
= 0.02, Figure). Multiple linear regression analysis revealed a significant positive association between DGLA levels and BV (unstandardized coefficient 0.01, 95% confidence interval 0.01 to 0.02,
p
< 0.01).

Conclusions:
Lower BV might be related to the presence of SVS with CE due to AF and DGLA level might be positively associated with BV.
Abstract WP202: Sleep Duration And Long Term Mortality After Stroke: A Nationwide Analysis
Authors: Hassani Sara , Ovbiagele Bruce , Markovic Daniela , Towfighi Amytis
Published: February 2023

Background and Objectives:
Sleep duration is a key marker of ideal cardiovascular health in the American Heart Association’s new Life’s Essential 8 construct, but studies on its relation to stroke are scarce. We assessed the association between sleep duration and mortality among self-reported stroke survivors in a nationally representative U.S. sample.

Methods:
Cross-sectional data (2005–2014) from the National Health and Nutrition Examination Surveys database in patients aged >=18 with a self-reported history of stroke (n=1,045) were linked to the 2015 National Death Index to determine the association between nightly sleep duration and mortality. Relationships between sleep duration (short: <7 hours, normal: 7-8 hours, long: >8 hours) and demographic characteristics were assessed. Relationships between sleep duration and mortality (all-cause and cardiovascular causes) were evaluated adjusting for demographic and clinical variables, with multivariable Cox regressions.

Results:
Among stroke survivors, prevalence of short sleep duration increased with younger age while prevalence of long sleep duration increased with older age (p<0.001). There were no significant differences in sleep duration between males and females (p=0.18). Prevalence of short sleep duration was higher among Hispanic and Non-Hispanic Blacks (p<0.0001). Stroke survivors with long sleep duration (vs normal) were more likely to be older, less educated, and overweight, and those with short sleep duration (vs normal) were more likely to be younger, non-White, and obese (age p<0.001, race/ethnicity p<0.001, education p=0.02, BMI p=0.001). Long sleep duration was associated with higher all-cause mortality in the unadjusted model (HR 1.92, 1.48-2.51, p<0.0001). After adjusting for demographic variables, this effect was attenuated (HR 1.35, 1.04-1.75, p=0.027). Once comorbidities were added to the model, the association was no longer significant. There were no significant associations between short sleep duration and all-cause mortality, and no significant associations between sleep duration and cardiovascular mortality.

Conclusion:
There is no independent association between sleep duration and all-cause or cardiovascular mortality after stroke.
Abstract WP205: Principal Diagnosis And Independent Predictors For 30-day Readmissions In Cryptogenic Stroke
Authors: Hussain Bilal , Bhavsar Dishang , Devarakonda Pradeep Kumar , Patibandla Saikrishna , Manoharan Suganya , Vasudevan Viswanath , Ayala-Rodriguez Cesar , Reddy Sarath
Published: February 2023

Background:
Cryptogenic stroke is defined as cerebral infraction that can’t be attributed to large artery atherosclerosis, small artery disease, or cardio-embolism, despite a standard cardiovascular and serologic workup. Our objective was to identify rates and causes for readmissions of cryptogenic stroke.

Methods:
A retrospective analysis was conducted using National Readmission Database 2018 with ICD-10 codes. Readmission rate and principal diagnosis for 30-day readmission for cryptogenic stroke were primary outcomes. Secondary outcomes were in-hospital mortality, and independent predictors of readmission. Multivariate logistic regression analysis was used for assessment.

Results:
Within 30 days, 21,418 out of 206,627 patients were readmitted, giving a 30-day readmission rate of 10.4%. For the index admissions, 49.9% were females, and mean age was 70 years. The in-hospital mortality rate for index admissions was 2.4% while it was 4.9% for the readmissions. The ten most common principal diagnosis for 30-day readmissions were subsequent admission for cryptogenic stroke (10.5%), sepsis (7.1%), acute kidney injury (3.2%), transient ischemic attack (1.9%), urinary tract infection (1.8%), aspiration pneumonitis (1.7%), hypertensive heart and chronic kidney disease (HHD/CKD) with heart failure (1.6%), left carotid artery stenosis/occlusion (1.5%), non-specific cerebral infarction (1.3%), and HHD with heart failure (1.2%). The independent predictors for readmission were heart failure, ischemic heart disease, ventricular arrhythmia, infective endocarditis, peripheral artery disease, venous thromboembolism, pulmonary embolism, and diabetes mellitus.

Conclusions:
Readmission rate for cryptogenic stroke is 10.4% within 30 days and is associated with higher mortality and costs. Most common principal diagnosis for readmission are cryptogenic stroke, sepsis, acute kidney injury, transient ischemic attack, urinary tract infection, and aspiration pneumonitis. The independent predictors for readmission are heart failure, ischemic heart disease, ventricular arrhythmia, infective endocarditis, peripheral artery disease, venous thromboembolism, pulmonary embolism, and diabetes mellitus.
Abstract WP207: Treatments Advanced, But Outcomes Stagnated In Young Adults With Acute Ischemic Stroke In Korea Between 2008 And 2019
Authors: Kim Jonguk , Kim Jun Y , Kang Jihoon , Kim Beom J , Han Moon-Ku , Park Tai H , Lee Ji Sung , Lee Keon-Joo , Kim Joon-Tae , Choi Kangho , Park Jong-moo , Kang Kyusik , Lee Soo Joo , Kim Jae G , Kim Dae Hyun , Cha Jae-kwan , Lee Kyung Bok , Lee Jun , Hong Keun-sik , Cho Yong-Jin , Park Hong-kyun , Lee Byung-Chul , Yu Kyung-Ho , Oh Mi S , Kim Dong-Eog E , Ryu Wi-sun , Choi Jay Chol , Kwon Jee-hyun , Kim Wook-joo , Shin Dong Ick I , Yum Kyu Sun , Sohn Sung-il , Hong Jeong-Ho , Lee Sanghwa , Lee Juneyoung , Bae Hee-joon ,   CRCS-K (Clinical Rsch Collaboration for Strokein Korea) investigators
Published: February 2023

Background:
Outcome improvement in young stroke patients is of great interest given their long life expectancy and substantial societal burden. We aimed to investigate whether the treatment advancement has been made and translated into outcome improvement in young patients with acute ischemic stroke (AIS).

Methods:
From a prospective multicenter stroke registry in South Korea, young AIS patients (aged 18-50) hospitalized between 2008 and 2019 were identified. The study period was divided into 4 epochs. The secular trends of patient characteristics, treatments, and outcomes adjusted for potential confounders were analyzed.

Results:
This study included 7,050 young AIS patients (mean age 43.1; men 71.9%) from 70,567 enrolled during the period. The mean age decreased from 43.6 years in 2008-2010 to 42.9 years in 2017-19 (P
trend
=.009). Obesity increased (40.1% to 49.0%), but current smoking decreased (53.1% to 42.8%). Other vascular risk factors and sex proportions did not change (P
trend
’s > 0.5). Onset-to-arrival time and door-to-puncture time for mechanical thrombectomy did not change (P
trend
’s > 0.5), but door-to-needle time for intravenous thrombolysis improved (P
trend
<.001). Acute and secondary stroke prevention treatments including intravenous thrombolysis (9.5% to 13.8%), mechanical thrombectomy (3.2% to 9.2%), dual antiplatelet therapy for minor stroke (26.6% to 48.0%), direct oral anticoagulant for atrial fibrillation (0.0% to 56.2%) and statins (71.5% to 91.2%) improved significantly (P
trend
’s <.01). For stroke outcomes, for which data were available since 2011, the proportions of 3-month modified Rankin Scale 0-1 (68.3% to 69.1%) and 0-2 (87.6% to 86.2%), one-year mortality (2.5% to 2.4%), and one-year stroke recurrence (4.4% to 5.3%) did not improve (adjusted P
trend
’s > 0.2).

Conclusions:
This study shows that the treatment improvements did not lead to outcome improvements in young AIS patients. The findings indicate that we should not be complacent with the current advances.
Abstract WP210: Aptamer Inhibitor Of Von Willebrand Factor Induces Thrombolysis And Improves Vascular Patency Upon Immediate And Delayed Treatment Of Stroke In An
In Vitro
Microfluidic Model
Authors: Mihalko Emily , Rassam Rassam , Nimjee Shahid M , Shea Susan
Published: February 2023

Von Willebrand factor (VWF) is critical in arterial thrombosis. Previous studies have shown that aptamer BB-031, a VWF inhibitor, induces thrombolysis
in vivo
in ischemic stroke models, making it a promising stroke therapeutic. We hypothesized that BB-031 will induce thrombolysis in an
ex vivo
ischemic stroke model and that advanced imaging techniques will provide mechanistic information. A microfluidic model was utilized to simulate ischemic stroke and drug delivery without disturbing the occluding thrombus. Heparinized whole blood was obtained from healthy volunteers (N=10). A gravity-based constant pressure microfluidic system mimicking arterial perfusion induced occlusive thrombosis at a collagen-coated region of stenosis. After resting for 0, 3, or 6 hours to allow retraction
in situ
thrombi were reperfused with blood containing 1692nM (~1mg/kg) BB-031, 0.7nM alteplase (ALT), 0.7nM tenecteplase (TEN), or vehicle 500um upstream of the thrombus using a separate inlet. Platelets were labelled prior to thrombus formation and reperfusion using fluorescent anti-CD41. Thrombolysis and patency were then monitored for 2hrs via outlet mass recording and z-stacked immunofluorescent imaging. Upon immediate reperfusion, 1692nM (~1mg/kg) BB-031 increased mean mass output by 0.250±0.629g compared to 0.031±0.065g with vehicle, 0.074±0.061g with ALT, and 0.101±0.150g with 0.7nM TEN. After a 3-hour retraction period, BB-031 reperfusion mean mass output was 0.951±1.279g compared to 0.301±0.380g with vehicle, 0.412±0.681g with ALT, and 0.569±0.714g with TEN. After 6-hours resting, reperfusion mass output increased by 1.354±1.433g with BB-031, 0.368±0.538g with vehicle, 0.158±0.195g with ALT, and 0.520±0.539g with TEN. Representative z-stacked renderings of the thrombus pre and post reperfusion from a 0-hour resting period show a volumetric decrease in thrombus size of 39% with BB-031 compared to 25% and 18% reduction with vehicle and ALT respectively in a donor-matched dataset. BB-031 improves patency in a microfluidic model of biofidelic thrombolysis compared to current standards of care, which is enhanced at 3 and 6 hours post-occlusion. This may be due to VWF-dependent lysis resulting in reduced thrombus volume.