Stroke Prevention Strategies Research Articles

Stroke prevention strategies in Africa: a scoping review protocol.

The objective of this scoping review is to map the existing strategies on methods and interventions for primary and secondary stroke prevention in Africa. Stroke is among the leading causes of disability globally. African nations have higher stroke mortality and case fatality rates than the industrialized world, leading to significant social and financial costs, which necessitates efficient preventative methods. Despite the high prevalence of stroke in Africa, the scope of stroke-prevention strategies in Africa is unknown. Consequently, mapping diverse approaches to preventing stroke in Africa could provide direction for future research into stroke prevention in Africa. This review will incorporate studies that report methods or strategies used for stroke prevention in Africa. All primary and gray literature will be considered for inclusion. No language or date restrictions will be applied. The JBI methodological framework for scoping reviews will be adopted for this scoping review. A 3-step search strategy consisting of an initial limited search, a full search, and a screening of the reference lists of all included articles will be undertaken. Databases such as CINAHL, Scopus, PubMed, PEDRo, DORIS, Global Health, Web of Science, and Open Access Thesis and Dissertations will be searched. All search results will be screened, and relevant data extracted by 2 independent reviewers. The findings will be presented in the final scoping review and illustrated in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. Figshare https://doi.org/10.6084/m9.figshare.21679904.v1.

Gut Microbiome and Stroke: a Bidirectional Mendelian Randomisation Study in East Asian and European Populations.

Observational studies have implicated the involvement of gut microbiome in stroke development. Conversely, stroke may disrupt the gut microbiome balance, potentially causing systemic infections exacerbated brain infarction. However, the causal relationship remains controversial or unknown. To investigate bidirectional causality and potential ethnic differences, we conducted a bidirectional two-sample Mendelian randomisation (MR) study in both East Asian (EAS) and European (EU) populations. Leveraging the hitherto largest genome-wide association study (GWAS) summary data from the MiBioGen Consortium (n=18 340, EU) and BGI (n=2524, EAS) for the gut microbiome, stroke GWAS data from the GIGASTROKE Consortium(264 655 EAS and 1 308 460 EU), we conducted bidirectional MR and sensitivity analyses separately for the EAS and EU population. We identified nominally significant associations between 85 gut microbiomes taxa in EAS and 64 gut microbiomes taxa in EU with stroke or its subtypes. Following multiple testing, we observed that genetically determined 1 SD increase in the relative abundance of species Bacteroides pectinophilus decreased the risk of cardioembolic stroke onset by 28% (OR 0.72 (95% CI 0.62 to 0.84); p=4.22e-5), and that genetically determined 1 SD increase in class Negativicutes resulted in a 0.76% risk increase in small vessel stroke in EAS. No significant causal association was identified in the EU population and the reverse MR analysis. Our study revealed subtype-specific and population-specific causal associations between gut microbiome and stroke risk among EAS and EU populations. The identified causality holds promise for developing a new stroke prevention strategy, warrants further mechanistic validation and necessitates clinical trial studies.

From A to E: Uniting vitamins against stroke risk-A systematic review and network meta-analysis.

Stroke represents a significant public health challenge, necessitating the exploration of preventive measures. This network meta-analysis aimed to assess the efficacy of different vitamin treatments compared to a placebo in preventing stroke. A systematic electronic search in databases including PubMed, EmBASE, Web of Science, clinicaltrials.gov, and Google Scholar until 31 May 2023 was conducted, to identify published studies investigating the association between vitamin intake and the risk of stroke. Pooled risk ratio (RR) with 95% confidence intervals (CIs) was calculated using a frequentist network meta-analysis. Furthermore, we ranked vitamins based on p-scores, facilitating a comparative assessment of their effectiveness in preventing stroke. A total of 56 studies, including 17 randomized controlled trials (RCTs) and 39 cohort studies were analyzed. Direct estimates obtained from network meta-analysis, we found that vitamin A (RR: .81 [.72-.91]), vitamin B-complex (RR:.85 [.74-.97]), vitamin B6 (RR: 79 [.68-.92]), folate (RR: .86 [.75-.97]), vitamin C (RR: .77 [.70-.85]) and vitamin D (RR: .73 [.64-.83]) were significantly associated with a decreased stroke risk. However, no significant association was observed for vitamin B2, vitamin B12, and vitamin E. Subsequent to network meta-analysis, vitamins were ranked in decreasing order of their efficacy in stroke prevention based on p-score, with vitamin D (p-score = .91), vitamin C (p-score = .79), vitamin B6 (p-score = .70), vitamin A (p-score = .65), vitamin B-complex (p-score = .53), folate (p-score = .49), vitamin B2 (p-score = .39), vitamin E (p-score = .28), vitamin B12 (.13) and placebo (.10). Our study has established noteworthy connections between vitamin A, vitamin B-complex, vitamin B6, folate, vitamin C, and vitamin D in the realm of stroke prevention. These findings add substantial weight to the accumulating evidence supporting the potential advantages of vitamin interventions in mitigating the risk of stroke. However, to solidify and validate these observations, additional research is imperative. Well-designed clinical trials or cohort studies are needed to further explore these associations and formulate clear guidelines for incorporating vitamin supplementation into effective stroke prevention strategies.

Seasonal Variations in Stroke and a Comparison of the Predictors of Unfavorable Outcomes among Patients with Acute Ischemic Stroke and Cardioembolic Stroke.

We investigated the seasonal variations in stroke in 4040 retrospectively enrolled patients with acute ischemic stroke (AIS) admitted between January 2011 and December 2022, particularly those with cardioembolic (CE) stroke, and compared predictors of unfavorable outcomes between AIS patients and CE stroke patients. The classification of stroke subtypes was based on the Trial of ORG 10172 in Acute Stroke Treatment. Stroke occurrence was stratified by seasons and weekdays or holidays. Of all AIS cases, 18% were of CE stroke. Of all five ischemic stroke subtypes, CE stroke patients were the oldest; received the most thrombolysis and thrombectomy; had the highest initial National Institutes of Stroke Scale (NIHSS) and discharge modified Rankin Scale (mRS) scores; and had the highest rate of in-hospital complications, unfavorable outcomes (mRS > 2), and mortality. The highest CE stroke prevalence was noted in patients aged ≥ 85 years (30.9%); moreover, CE stroke prevalence increased from 14.9% in summer to 23.0% in winter. The main predictors of death in patients with CE stroke were age > 86 years, heart rate > 79 beats/min, initial NIHSS score > 16, neutrophil-to-lymphocyte ratio (NLR) > 6.4, glucose > 159 mg/dL, cancer history, in-hospital complications, and neurological deterioration (ND). The three most dominant factors influencing death, noted in not only patients with AIS but also those with CE stroke, are high initial NIHSS score, ND, and high NLR. We selected the most significant factors to establish nomograms for predicting fatal outcomes. Effective heart rhythm monitoring, particularly in older patients and during winter, may help develop stroke prevention strategies and facilitate early AF detection.

Percutaneous left atrial appendage occlusion in mitral valve disease: A Nationwide Readmission Database analysis

BackgroundPercutaneous left atrial appendage occlusion (LAAO) has emerged as a non-pharmacologic alternative to oral anticoagulation in reducing stroke risk in AF patients. However, patients with mitral valve disease (MVD), who are expected to have a significantly greater risk of left atrium (LA) thrombus formation and embolic stroke were excluded from randomized trials examining percutaneous LAAO. To address this gap, we present a national registry analysis of the use of LAAO among patients with MVD. MethodsUsing the National Readmissions Database, we performed a retrospective review of all hospitalizations for LAAO identified between September 2015 and November 2019. Of these, patients with ICD-10 codes for MVD were identified. Propensity matched (PSM) analysis was used to compare patients with MVD with a matched sample of patients undergoing LAAO with non-valvular AF. Outcomes examined included all-cause mortality, stroke, major bleeding, pericardial effusion (PE), and tamponade. Results51,540 patients who underwent LAAO without a history of MVD and 3777 with a history of MVD were identified. Crude analysis demonstrated the odds of mortality, PE, and cardiac tamponade during index hospitalization to be higher in the MVD group. The length of stay and cost of index hospitalization were also slightly greater for the MVD group. A sample of 7649 patients (MVD: 3777 MVD and no MVD: 3872) were selected for PSM analysis with similar comorbidities across the two groups. In the PSM comparison, MVD was associated with higher risk of PE. The MVD group had a slightly higher rate of readmissions the association with PE remained at 30-day readmission (OR: 2.099 [1.360–3.238], p-value: <0.001). ConclusionTo our knowledge, this is the first study examining the use of LAAO among MVD patients. Our findings suggest that patients with MVD who underwent LAAO had a higher risk of post-procedural PE without an increase in mortality, stroke, or major bleeding. These results provide a rationale for considering LAAO as part of the stroke prevention strategy among patients with valvular AF.

Acute ischemic stroke prediction and predictive factors analysis using hematological indicators in elderly hypertensives post-transient ischemic attack

Elderly hypertensive patients diagnosed with transient ischemic attack (TIA) are at a heightened risk for developing acute ischemic stroke (AIS). This underscores the critical need for effective risk prediction and identification of predictive factors. In our study, we utilized patient data from peripheral blood tests and clinical profiles within hospital information systems. These patients were followed for a three-year period to document incident AIS. Our cohort of 11,056 individuals was randomly divided into training, validation, and testing sets in a 5:2:3 ratio. We developed an XGBoost model, developed using selected indicators, provides an effective and non-invasive method for predicting the risk of AIS in elderly hypertensive patients diagnosed with TIA. Impressively, this model achieved a balanced accuracy of 0.9022, a recall of 0.8688, and a PR-AUC of 0.9315. Notably, our model effectively encapsulates essential data variations involving mixed nonlinear interactions, providing competitive performance against more complex models that incorporate a wider range of variables. Further, we conducted an in-depth analysis of the importance and sensitivity of each selected indicator and their interactions. This research equips clinicians with the necessary tools for more precise identification of high-risk individuals, thereby paving the way for more effective stroke prevention and management strategies.

Prevalence of stroke-related risk factors in Albania: a single-center experience.

Stroke, a prominent global cause of mortality and disability, is broadly categorized into ischemic and hemorrhagic types. An epidemiological survey of stroke and its risk factors can help identify individuals at higher risk and therefore promote stroke prevention strategies. The aim of this study was to estimate the current prevalence of stroke and evaluate stroke-associated risk factors in Albania. This was a single-center retrospective analysis conducted in Albania for the period from May 2015 to September 2021. Data were collected retrospectively through hospital records. Stroke was defined as sudden onset of a nonconvulsive and focal neurological deficit, and ischemic stroke was diagnosed using brain computed tomography (CT), magnetic resonance (MR) imaging, or both. We examined patient history characteristics encompassing demographics, stroke history, conventional vascular risk factors, and lifestyle-related risk factors. The mean age of the 3860 patients was 74.6 ±10.4 years, and 73.5% were men. The prevalence of carotid stenosis, arrhythmia, obesity, and hypertension was significantly higher in males than in females (p < 0.001). Out of the 3860 patients in the study cohort, 641 (16.6%) subjects died, while 335 (8.7%) patients achieved complete recovery. Hemiparesis was observed in 386 (10%) patients and hemiplegia in 868 (22.4%) patients. Our analysis underscores the male predominance (2.2 : 1) in stroke cases. Carotid and vertebral artery stenosis is a significant factor, emphasizing the life-saving potential of early intervention. Social and economic factors in Albania pose challenges, demanding comprehensive strategies. Prospective trials are crucial to explore intervention efficacy, and timing, and address socioeconomic impacts on timely stroke management.

New-onset as opposed to established atrial fibrillation as a risk factor for incident stroke

BackgroundAtrial fibrillation (AF) is an established risk factor for acute ischemic stroke (AIS). It remains unclear if new-onset AF confers a higher risk of AIS than longer-standing AF. MethodsWe retrospectively analyzed all stroke-free patients who underwent transthoracic echocardiography (TTE) in the Henry Ford Health System between March 6 and September 6, 2016. Incident AIS and new-onset AF were ascertained by the presence of new diagnostic codes in the electronic medical record over a follow-up period of up to 5 years. Cox proportional hazards regression was used to identify risk factors for new-onset AF or AIS. ResultsOf 7310 patients who underwent baseline TTE the mean age was 65 years, 54% were female, 51% were Caucasian, and 46% had left atrial enlargement (LAE). Of at-risk patients, 10.9% developed new-onset AF and 2.9% experienced incident AIS. The risk of new-onset AF among at-risk patients was 3.1 times higher among patients with any degree of LAE compared to those with normal LA size (95% CI 2.6–3.6, P < 0.0001). New-onset AF, more than established AF, in turn had a powerful association with incident AIS. The cumulative 5-year risk of AIS was 3.5% in those without AF, 5.9% in those with established AF prior to TTE, and 20.1% in those with new-onset AF (P < 0.0001). In multivariable analysis new-onset AF had the strongest association with incident AIS (P < 0.0001), followed by increasing age (P = 0.0025), black race (P = 0.0032), and smoking (P = 0.0063). ConclusionsNew-onset AF has a strong relationship with incident AIS. LAE was present in nearly half of stroke-free patients undergoing TTE, and was associated with a significantly higher likelihood of new-onset AF during follow-up. Vigilant cardiac monitoring for AF in individuals with LAE, coupled with the timely initiation of anticoagulation, may be an important strategy for the primary prevention of AF-related stroke.

Prevalence and associated factors of mild cognitive impairment among middle-aged and older adults: Results of the first phase of Ardakan Cohort Study on Aging.

Data on mild cognitive impairment (MCI) in low- to middle-income countries are still being determined, despite the fact that most future older adults are expected to reside in these regions. This study aimed to investigate the prevalence and associated factors of MCI in Iran. A cross-sectional study was conducted on 4938 community-dwelling subjects aged 50 years or above in the first wave of the Ardakan Cohort Study on Aging. MCI was evaluated using the Mini-Mental State Examination (MMSE) and the Abbreviated Mental Test Score (AMTS) in literate and illiterate individuals. The relationship between factors associated with the odds of MCI was assessed through logistic regression. The prevalence of MCI among all participants, the literates and illiterates, was 15.8%, 6.3%, and 36.4%, respectively. It was found that failure to accomplish any of the MMSE or AMTS items was significantly related to MCI (p < 0.001). Age ([odds ratio (OR): 1.05; p < 0.001 in the literates], [OR: 1.06; p < 0.001 in the illiterates]), sex (OR: 0.13; p < 0.001 in the illiterates), history of stroke ([OR: 2.86; p = 0.006 in the literates], [OR: 2.04; p = 0.045 in the illiterates]), and depression ([OR: 1.87; p < 0.001 in the literates], [OR: 1.41; p = 0.008 in the illiterates]) were significantly associated with MCI. This study highlights the significant associations between age, education, depression, stroke, and MCI in Iranian participants. These findings emphasize the need for targeted interventions in low-literacy populations, mental health screening, and stroke prevention strategies to mitigate the burden of MCI and enhance cognitive health.

Detection and Diagnostic Accuracy of Cardiac Arrhythmias Using Wearable Health Devices: A Systematic Review.

Photoplethysmography (PPG) is the wearable devices' most widely used technology for monitoring heart rate. The systematic review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards and guidelines. This systematic review seeks to establish the effects of wearable health devices on cardiac arrhythmias concerningtheir impacton the personalization of cardiac management, their refining effect on stroke prevention strategies, and their influence on research and preventive care of cardiac arrhythmiasand their re-evaluation of the patient-physician relationship. The population, exposure, control, outcomes, and studies (PECOS) criteria were used in the systematic review. This review considered studies that covered the tests conducted on individuals who presented with cardiovascular diseases (CVD) and also healthy people. The intervention for studies included wearable health devices that could detect and diagnose cardiac arrhythmias. The study considered articles that reported on the personalization of cardiac management, stroke prevention strategies, influence in research and preventive care of cardiac arrhythmias, and the re-evaluation of the patient-physician relationship. Two independent researchers were used in the extraction of the data. In case of dispute, the issue was resolved using a third party. The study's quality analysis was conducted using AXIS. The management of atrial fibrillation (AF) lies heavily in the prevention of stroke. The accuracy being reported in the prediction of arrhythmias and the monitoring of heart rates makes wearable devices an efficient means to personalize health care. Personalization of health and treatment in preventing and managing arrhythmias becomes possible due to the portability of smart wearable devices. However, limitations may be observed due to the high costs incurred in their purchase and use. Using smart wearable devices for the detection of cardiac arrhythmias was very significant.

Comprehensive understanding of stroke risk, prognosis, and preventive strategies for type 2 diabetes

Stroke is a serious and disabling disease with a high mortality rate that is becoming increasingly common worldwide, posing a serious threat to the health and quality of life of patients. Type 2 diabetes plays a special role in increasing the risk of stroke, which not only increases the risk of developing a stroke, but also negatively affects the outcome and the possibility of recurrent strokes.In order to prevent stroke, systematic action is necessary, including the correction of risk factors and the use of effective medications. One such drug is pioglitazone. Many studies support its effectiveness in reducing the risk of cardiovascular events, including stroke, for both secondary and primary prevention.Pioglitazone may be particularly beneficial for patients at high risk of cardiovascular disease and those with a history of ischemic brain damage. Despite the known side effects, its benefits in preventing stroke outweigh the possible disadvantages.This review provides important aspects of the role of type 2 diabetes mellitus in increasing the risk of stroke and discusses the prospects for the use of pioglitazone as a drug therapy affecting stroke risk and prognosis.

Selection of Non-vitamin K Antagonist Oral Anticoagulant for Stroke Prevention in Atrial Fibrillation Based on Patient Profile: Perspectives from Vietnamese Experts. Part 1.

In Asia, especially Vietnam, AF is a common arrhythmia and is linked to a higher risk of stroke and systemic embolism. Anticoagulation therapy for stroke prevention in AF patients can result in bleeding complications. To effectively manage AF, adopting appropriate anticoagulation and addressing modifiable risk factors are crucial. Vietnamese clinicians are particularly interested in non-vitamin K antagonist oral anticoagulants (NOACs), a recent development in AF treatment. However, the lack of head-to-head trials comparing NOACs makes selecting a specific NOAC challenging. This review aims to provide a comprehensive overview of the available clinical evidence on NOACs for stroke prevention in AF to assist clinicians in making informed decisions and improving treatment outcomes in patients with AF. The first part of this review will present the current landscape of AF in Vietnam, focusing on AF prevalence and highlighting gaps in clinical practice. Furthermore, this part extensively discusses the anticoagulation strategy for both primary and secondary stroke prevention in AF.

Racial disparities in stroke incidence in the Women's Health Initiative: Exploring biological, behavioral, psychosocial, and social risk factors

Background– Disparities in incident stroke risk among women by race and ethnicity persist. Few studies report the distribution and association of stroke risk factors by age group among a diverse sample of women. Methods– Data from the Women's Health Initiative (WHI) Observational Study collected between 1993 and 2010 were used to calculate cumulative stroke incidence and incidence rates among non-Hispanic African American (NHAA), non-Hispanic white (NHW), and Hispanic white or African American (HWAA) women by age group in participants aged ≥50 years at baseline (N = 77,247). Hazard ratios (HRs) and 95% CIs for biological, behavioral, psychosocial, and socioeconomic factors overall and by race or ethnicity were estimated using sequential Cox proportional hazard regression models. Results– Average follow-up time was 11.52 (SD, 3.48) years. The incident stroke rate was higher among NHAA (306 per 100,000 person-years) compared to NHW (279/100,000py) and HWAA women (147/100,000py) overall and in each age group. The disparity was largest at ages >75 years. The association between stroke risk factors (e.g., smoking, BMI, physical activity) and incident stroke varied across race and ethnicity groups. Higher social support was significantly associated with decreased stroke risk overall (HR:0.84, 95% CI, 0.76, 0.93); the degree of protection varied across race and ethnicity groups. Socioeconomic factors did not contribute additional stroke risk beyond risk conferred by traditional and psychosocial factors. Conclusions– The distribution and association of stroke risk factors differed between NHAA and NHW women. There is a clear need for stroke prevention strategies that address factors driving racial disparities in stroke risk.

Safety and efficacy of direct oral anticoagulants in stroke prevention in patients with atrial fibrillation complicated with anemia and/or thrombocytopenia: a retrospective cohort study

BackgroundThere are limited data about the clinical benefits and harm of direct oral anticoagulants (DOACs) in stroke prevention in patients with atrial fibrillation (AF) complicated with anemia or thrombocytopenia.MethodsThis is a multi-center retrospective cohort study involving 5469 AF patients from 15 hospitals in China. Patients were divided into three groups according to hemoglobin and platelet levels: Group 1 (hemoglobin male ≥ 130 g/L; female ≥ 120 g/L and platelet ≥ 100 × 109/L), Group 2 (hemoglobin male < 130 g/L; female < 120 g/L or platelet < 100 × 109/L), and Group 3 (hemoglobin male < 130 g/L; female < 120 g/L and platelet < 100 × 109/L). Patients in each category are further divided into two groups according to their stroke prevention strategies: rivaroxaban or dabigatran. Clinical results include major, minor, total bleeding, thrombosis, and the composite outcome of major bleeding and thrombosis.ResultsHigher hemoglobin levels were associated with a reduced risk of total bleeding and major bleeding, while platelet counts were not associated with any event. Compared with Group 1, Group 2 had a higher risk of major bleeding (aOR 1.70, 95%CI 1.12–2.57, P = 0.012), and the composite endpoint of major bleeding and thrombosis (aOR 1.70, 95%CI 1.19–2.44, P = 0.004). Compared with Group 1, Group 3 had a higher total bleeding risk (aOR 2.15, 95%CI 1.14–4.05, P = 0.018). Compared with dabigatran, rivaroxaban was associated with higher composite risk in Group 1 (aOR 2.91, 95% CI 1.66–5.16, P < 0.001) and Group 2 (aOR 3.05, 95%CI 1.46–6.39, P = 0.003), but there was no significant difference in Group 3 (aOR 1.78, 95%CI 0.23—13.54, P = 0.577).ConclusionsHigher hemoglobin levels are associated with a reduced risk of total bleeding and major bleeding in patients with AF. Dabigatran was associated with better clinical outcomes than rivaroxaban in patients with anemia or thrombocytopenia but not in those with anemia and thrombocytopenia.

Improving Stroke Risk Factor Management Focusing on Health Disparities and Knowledge Gaps.

Stroke is a leading cause of death and disability in the United States and worldwide, necessitating comprehensive efforts to optimize stroke risk factor management. Health disparities in stroke incidence, prevalence, and risk factor management persist among various race/ethnic, geographic, and socioeconomic populations and negatively impact stroke outcomes. This review highlights existing literature and guidelines for stroke risk factor management, emphasizing health disparities among certain populations. Moreover, stroke risk factors for special groups, including the young, the very elderly, and pregnant/peripartum women are outlined. Strategies for stroke risk factor improvement at every level of the health care system are discussed, from the individual patient to providers, health care systems, and policymakers. Improving stroke risk factor management in the context of the social determinants of health, and with the goal of eliminating inequities and disparities in stroke prevention strategies, are critical steps to reducing the burden of stroke and equitably improving public health.

Assessing the causal effect of genetically predicted metabolites and metabolic pathways on stroke

BackgroundStroke is a common neurological disorder that disproportionately affects middle-aged and elderly individuals, leading to significant disability and mortality. Recently, human blood metabolites have been discovered to be useful in unraveling the underlying biological mechanisms of neurological disorders. Therefore, we aimed to evaluate the causal relationship between human blood metabolites and susceptibility to stroke.MethodsSummary data from genome-wide association studies (GWASs) of serum metabolites and stroke and its subtypes were obtained separately. A total of 486 serum metabolites were used as the exposure. Simultaneously, 11 different stroke phenotypes were set as the outcomes, including any stroke (AS), any ischemic stroke (AIS), large artery stroke (LAS), cardioembolic stroke (CES), small vessel stroke (SVS), lacunar stroke (LS), white matter hyperintensities (WMH), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), transient ischemic attack (TIA), and brain microbleeds (BMB). A two‐sample Mendelian randomization (MR) study was conducted to investigate the causal effects of serum metabolites on stroke and its subtypes. The inverse variance-weighted MR analyses were conducted as causal estimates, accompanied by a series of sensitivity analyses to evaluate the robustness of the results. Furthermore, a reverse MR analysis was conducted to assess the potential for reverse causation. Additionally, metabolic pathway analysis was performed using the web-based MetOrigin.ResultsAfter correcting for the false discovery rate (FDR), MR analysis results revealed remarkable causative associations with 25 metabolites. Further sensitivity analyses confirmed that only four causative associations involving three specific metabolites passed all sensitivity tests, namely ADpSGEGDFXAEGGGVR* for AS (OR: 1.599, 95% CI 1.283–1.993, p = 2.92 × 10−5) and AIS (OR: 1.776, 95% CI 1.380–2.285, p = 8.05 × 10−6), 1-linoleoylglycerophosph-oethanolamine* for LAS (OR: 0.198, 95% CI 0.091–0.428, p = 3.92 × 10−5), and gamma-glutamylmethionine* for SAH (OR: 3.251, 95% CI 1.876–5.635, p = 2.66 × 10−5), thereby demonstrating a high degree of stability. Moreover, eight causative associations involving seven other metabolites passed both sensitivity tests and were considered robust. The association result of one metabolite (glutamate for LAS) was considered non-robust. As for the remaining metabolites, we speculate that they may potentially possess underlying causal relationships. Notably, no common metabolites emerged from the reverse MR analysis. Moreover, after FDR correction, metabolic pathway analysis identified 40 significant pathways across 11 stroke phenotypes.ConclusionsThe identified metabolites and their associated metabolic pathways are promising circulating metabolic biomarkers, holding potential for their application in stroke screening and preventive strategies within clinical settings.

Effectiveness of Cerebral Embolic Protection in Transcatheter Aortic Valve Replacement with High Aortic Valve Calcium Burden

Abstract Background The use of a cerebral embolic protection device (CEPD) during transcatheter aortic valve replacement (TAVR) has not been shown to be effective in preventing stroke in the PROTECTED-TAVR randomized controlled trial. However, whether CEPD may specifically benefit patients with high aortic valve calcium burden has not been studied. Purpose This study aimed to determine the effectiveness of CEPD in preventing cerebrovascular events during TAVR in patients with high aortic valve calcium scores (AVCS) (&amp;gt;2000 AU in men and &amp;gt;1300 AU in women) detected on baseline computed tomography. Methods We retrospectively analyzed 3505 patients who underwent transfemoral TAVR at a single center between 2016-2020 (Figure 1a). Baseline demographic, clinical, and procedural characteristics were stratified by CEPD use and AVCS (high vs. low). We performed Cox Proportional Hazards regression analysis to examine whether the use of CEPD in patients with high AVCS was associated with a lower rate of cerebrovascular events (stroke or transient ischemic attack) within 30 days (primary outcome) after adjusting for baseline characteristics. Results We stratified our study cohort into four subgroups: low AVCS without CEPD (n=1163), low AVCS with CEPD (n=633), high AVCS without CEPD (n=1081), and high AVCS with CEPD (n=628). Patients for whom CEPD was used in high AVCS group had lower prevalence of peripheral arterial disease compared with no CEPD use. Otherwise, there were no significant differences in the baseline characteristics between patients with and without CEPD in either the low or high AVCS subgroups (Table). In adjusted analysis, CEPD use (HR 1.30 [95% CI, 0.64-2.65)] or high AVCS (HR 1.16 [95% CI, 0.64-2.02)] were not associated with a decreased rate of primary outcome (Figure 1b). Conclusion This study indicates that CEPD use is not associated with lower cerebrovascular events after TAVR, even in patients with a high aortic valve calcium burden. Further research is needed to identify effective stroke prevention strategies for this patient population.Study design and Cox regression analysesBaseline Characteristics and Outcomes

Abstract 12823: As Anticoagulation Use Increases, Embolic Events Downtrend in Atrial Fibrillation Hospitalizations

Background: Direct oral anticoagulants and Left atrial appendage closure (LAAC) were approved for use in 2010 and 2015, respectively. Data on temporal changes in stroke prevention strategies and rates of embolic complications in atrial fibrillation (AF) in the 2010s decade are limited. Aims: Describe trends in long-term anticoagulation (AC), LAAC use, and in-hospital AF associated ischemic stroke (IS), transient ischemic attacks (TIA), and systemic embolic events (SEE) between 2010 and 2019. Methods: The national inpatient database was used to identify patients with AF from 2010 to 2019. Data were divided into 2 eras: 2010-2014 and 2015-2019. Results: A total of 40,787,136 inpatients with AF were identified: prevalence increased from 18,594,372 in 2010 to 2014 (46%; mean [SD] age 75.5 [12.0] years; 50.3% male) to 22,192,764 in 2015 to 2019 (54%; mean [SD] age 75.1 [11.8] years; 52.5% male). There was a marked increase in long-term AC use (27.2% to 40.2%; P=0.001) and rates of percutaneous LAAC procedures (0.01% to 0.6%; P &lt;0.001) from 2015 to 2019. IS rates among patients with AF increased from 2010 to 2014 (3.5% to 3.8%; P=0.04), with no significant temporal change from 2015 to 2019 (P=0.84). TIA rates declined from 2010 to 2014 (1.2% to 1.0%; P=0.017) and continued a downtrend from 2015 to 2019 (0.9% to 0.7%; P=0.002). There was no temporal change in SEE or the composite outcome of all embolic events from 2010 to 2014, followed by a decline from 2015 to 2019 in SEE (0.5% to 0.4%; P 0.012) and all embolic events (5.1% to 4.8%; P 0.026) ( Figure 1 ). Mean rates of major bleeding events increased from 5.7% in 2010-2014 to 9.1% in 2015-2019 (P &lt;0.001). Conclusion: In an inpatient AF population, the composite outcome of all embolic events and specifically SEE downtrend from 2015 to 2019, likely due to increased AC use. Further data assessing the risk-benefit ratio of available therapies for stroke prevention in inpatients with AF - AC and LAAC - are needed to optimize personalized strategies.

Abstract 072: Risk Factors for Developing Ischemic Strokes While Taking Non‐Vitamin K Antagonist Oral Anticoagulants

Introduction Over the past decade, non‐vitamin K antagonist oral anticoagulants (NOACs) have replaced warfarin as the initial strategy for stroke prevention in non‐valvular atrial fibrillation. However, ischemic strokes occurring in patients taking NOACs are becoming increasingly more frequent. In this study, we aimed to determine the clinical, echocardiographic, and neuroimaging markers associated with developing ischemic strokes in patients taking NOACs for atrial fibrillation. Methods Among atrial fibrillation patients on NOACs with and without ischemic stroke, brain MRIs were reviewed for the presence of neuroimaging markers of small vessel disease. Transthoracic echocardiography reports were reviewed to obtain left atrial volumes, presence of left ventricular hypertrophy, ejection fractions, and presence of wall motion abnormalities. Clinical and radiologic variables with significant differences between groups were entered into a multivariable regression model to determine predictors of ischemic stroke. In the ischemic stroke group, a Cox regression analysis was constructed to determine predictors of ischemic stroke recurrence during follow‐up. Results 112 patients with ischemic stroke and 94 controls (free of ischemic stroke) were included in the study. The mean age (77±9 years vs. 74±11 years, p = 0.13) and proportion of patients with CHA2DS2‐VASc&gt;2 were similar between controls and ischemic stroke patients (82% vs. 83%, p = 0.86). The variables that were significantly different between groups included apixaban use, dabigatran use, prior cerebrovascular events, hemoglobin A1c (HbA1c), left ventricular hypertrophy, left atrial volume index, and severe white matter hyperintensities. After multivariable adjustment, prior cerebrovascular events (aOR 23.86, 95% CI [6.02–94.48]), HbA1c levels (aOR 2.36, 95% CI [1.39–3.99]), left ventricular hypertrophy (aOR 2.73, 95% CI [1.11–6.71]) and left atrial volume index (aOR 1.05, 95% CI [1.01–1.08]) increased the risk of stroke, whereas apixaban use appeared to decrease the risk (aOR 0.38, 95% CI [0.16–0.92]). Among patients with ischemic stroke, there were 103 survivors, 82 (80%) of which had follow‐up data. The median follow‐up duration for these patients was 2.6 (0.5–4.7) years. Of these 82 patients, 11 (13%) experienced an ischemic stroke during the follow‐up period. Malignancy was associated with ischemic stroke recurrence (aHR 4.90, 95% CI [1.35–18.42]) after adjustment for age and chronic renal failure. Conclusion Prior cerebrovascular events, diabetes, left ventricular hypertrophy, and left atrial size are associated with the development of ischemic stroke among NOAC users. Future studies should aim to investigate nonpharmacological stroke prevention strategies in patients with the vascular risk factors and echocardiographic risk markers identified in the present study.

Cost-effectiveness of left atrial appendage closure for stroke prevention in atrial fibrillation: a systematic review appraising the methodological quality

BackgroundThe increasing global prevalence of atrial fibrillation (AF) has led to a growing demand for stroke prevention strategies, resulting in higher healthcare costs. High-quality economic evaluations of stroke prevention strategies can play a crucial role in maximising efficient allocation of resources. In this systematic review, we assessed the methodological quality of such economic evaluations.MethodsWe searched electronic databases of PubMed, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and Econ Lit to identify model-based economic evaluations comparing the left atrial appendage closure procedure (LAAC) and oral anticoagulants published in English since 2000. Data on study characteristics, model-based details, and analyses were collected. The methodological quality was evaluated using the modified Economic Evaluations Bias (ECOBIAS) checklist. For each of the 22 biases listed in this checklist, studies were categorised into one of four groups: low risk, partial risk, high risk due to inadequate reporting, or high risk. To gauge the overall quality of each study, we computed a composite score by assigning + 2, 0, − 1 and − 2 to each risk category, respectively.ResultsIn our analysis of 12 studies, majority adopted a healthcare provider or payer perspective and employed Markov Models with the number of health states varying from 6 to 16. Cost-effectiveness results varied across studies. LAAC displayed a probability exceeding 50% of being the cost-effective option in six out of nine evaluations compared to warfarin, six out of eight evaluations when compared to dabigatran, in three out of five evaluations against apixaban, and in two out of three studies compared to rivaroxaban. The methodological quality scores for individual studies ranged from 10 to − 12 out of a possible 24. Most high-risk ratings were due to inadequate reporting, which was prevalent across various biases, including those related to data identification, baseline data, treatment effects, and data incorporation. Cost measurement omission bias and inefficient comparator bias were also common.ConclusionsWhile most studies concluded LAAC to be the cost-effective strategy for stroke prevention in AF, shortcomings in methodological quality raise concerns about reliability and validity of results. Future evaluations, free of these shortcomings, can yield stronger policy evidence.