Higher Risk Of Intracerebral Hemorrhage Research Articles

Association of Aspirin Use With Risk of Intracerebral Hemorrhage in Patients Without History of Stroke or Transient Ischemic Attack in the UK Biobank

Background: The association between aspirin use and the risk of intracerebral hemorrhage (ICH) among individuals without previous stroke events is inconclusive. Aim: We investigated the association between regular aspirin use and ICH risk in middle-aged and older adults without previous stroke or transient ischemic attack (TIA). Methods: This prospective population-based study included participants older than 40 years with no history of stroke or TIA from the UK Biobank. The main exposure was regular aspirin use. Cox regression analyses and propensity score matching analyses estimated the hazard ratios (HRs) for aspirin use for incident fatal and non-fatal ICH. We conducted prespecified subgroup analyses for selecting individuals at high risk of ICH when using aspirin. Multiple sensitivity analyses were performed to test the robustness of our results. Results: A total of 449,325 participants were included into final analyses (median [IQR] age 58 [50 - 63] years, 54.6% females), of whom 58,045 reported aspirin use. During a median follow-up of 12.75 (IQR 12.03 – 13.47) years, 1,557 (0.3%) incident ICH cases were identified, of which 399 (25·6%) were fatal. Aspirin was not associated with increased risk of overall (HR 1.11, 95% CI 0.95 – 1.27, P = 0.188), fatal (HR 1.03, 95% CI 0.78 – 1.36, P = 0.846) and non-fatal (HR 1.12, 95% CI 0.95 – 1.33, P = 0.186) ICH. Propensity score matching analysis showed similar results. Subgroup analysis indicated that aspirin use in individuals older than 65 years or with concurrent anticoagulant use was correlated with increased risk of ICH. Conclusions: In this large cohort study of middle-aged and older adults without stroke or TIA events, there was no significant association between aspirin use and ICH risk in the real-world setting. However, it is possible that aspirin use in those aged over 65 years and concurrent anticoagulant treatment may increase the risk of ICH.

Impact of intensive blood pressure lowering after multiple-attempt endovascular thrombectomy: A secondary analysis of the OPTIMAL-BP trial.

Multiple attempts of thrombectomy have been linked to a higher risk of intracerebral hemorrhage and worsened functional outcomes, potentially influenced by blood pressure (BP) management strategies. Nonetheless, the impact of intensive BP management following successful recanalization through multiple attempts remains uncertain. This study aimed to investigate whether conventional and intensive BP managements differentially affect outcomes according to multiple-attempt recanalization (MAR) and first-attempt recanalization (FAR) groups. In this secondary analysis of the OPTIMAL-BP trial, which was a comparison of intensive (systolic BP target: <140 mm Hg) and conventional (systolic BP target = 140-180 mm Hg) BP managements during the 24 h after successful recanalization, we included intention-to-treat population of the trial. Patients were divided into the MAR and the FAR groups. We examined a potential interaction between the number of thrombectomy attempts (MAR and FAR groups) and the effect of BP managements on clinical and safety outcomes. The primary outcome was functional independence at 3 months. Safety outcomes were symptomatic intracerebral hemorrhage within 36 h and mortality within 3 months. Of the 305 patients (median = 75 years), 102 (33.4%) were in the MAR group and 203 (66.6%) were in the FAR group. The intensive BP management was significantly associated with a lower rate of functional independence in the MAR group (intensive, 32.7% vs conventional, 54.9%, adjusted odds ratio (OR) = 0.33, 95% confidence interval (CI) = 0.12-0.90, p = 0.03). In the FAR group, the proportion of patients with functional independence was not significantly different between the BP managements (intensive, 42.5% vs conventional, 54.2%, adjusted OR = 0.73, 95% CI = 0.38-1.40). Incidences of symptomatic intracerebral hemorrhage and mortality rates were not significantly different according to the BP managements in both MAR and FAR groups. Among stroke patients who received multiple attempts of thrombectomy, intensive BP management for 24 h resulted in a reduced chance of functional independence at 3 months and did not reduce symptomatic intracerebral hemorrhage following successful reperfusion.

APOE ε4 and Intracerebral Hemorrhage in Patients With Brain Arteriovenous Malformation

Intracerebral hemorrhage (ICH) is a serious complication of brain arteriovenous malformation (AVM). Apolipoprotein E (APOE) ε4 is a well-known genetic risk factor for ICH among persons without AVM, and cerebral amyloid angiopathy is a vasculopathy frequently observed in APOE ε4 carriers that may increase the risk of ICH. To assess whether APOE ε4 is associated with a higher risk of ICH in patients with a known AVM. This cross-sectional study including 412 participants was conducted in 2 stages (discovery and replication) using individual-level data from the UK Biobank (released March 2012 and last updated October 2023) and the All of Us Research Program (commenced on May 6, 2018, with its latest update provided in October 2023). The occurrence of AVM and ICH was ascertained at the time of enrollment using validated International Classification of Diseases, Ninth Revision and Tenth Revision, codes. Genotypic data on the APOE variants rs429358 and rs7412 were used to ascertain the ε status. For each study, the association between APOE ε4 variants and ICH risk was assessed among patients with a known AVM by using multivariable logistic regression. The discovery phase included 253 UK Biobank participants with known AVM (mean [SD] age, 56.6 [8.0] years, 119 [47.0%] female), of whom 63 (24.9%) sustained an ICH. In the multivariable analysis of 240 participants of European ancestry, APOE ε4 was associated with a higher risk of ICH (odds ratio, 4.58; 95% CI, 2.13-10.34; P < .001). The replication phase included 159 participants with known AVM enrolled in All of Us (mean [SD] age, 57.1 [15.9] years; 106 [66.7%] female), of whom 29 (18.2%) sustained an ICH. In multivariable analysis of 101 participants of European ancestry, APOE ε4 was associated with higher risk of ICH (odds ratio, 4.52; 95% CI, 1.18-19.38; P = .03). The results of this cross-sectional study of patients from the UK Biobank and All of Us suggest that information on APOE ε4 status may help identify patients with brain AVM who are at particularly high risk of ICH and that cerebral amyloid angiopathy should be evaluated as a possible mediating mechanism of the observed association.

Abstract TMP77: Oral Health as a Risk Factor for Spontaneous Intracerebral Hemorrhage: A Mendelian Randomization Analysis

Background: Poor oral health is a highly prevalent and modifiable risk factor that is associated with higher risk of cardiovascular disease, including ischemic stroke. However, the relationship between oral health and spontaneous intracerebral hemorrhage (ICH) has not been studied. We tested the hypothesis that genetically-determined poor oral health increases the risk of ICH. Methods: We conducted a two-sample Mendelian Randomization (MR) study using summary statistics from the largest genome-wide associations studies of oral health and ICH conducted to date. As genetic instruments (e.g., genetic risk variants for oral health), we identified 105 independent single nucleotide polymorphisms known to be associated with higher risk of caries, dentures and missing teeth at genome wide levels (p&lt;5x10 -8 ). The primary analysis employed summary statistics-based MR to assess the relationship between poor oral health and risk of ICH in any brain location. Secondary analyses evaluated deep and lobar ICH separately. Results: The primary analysis using the inverse variance-weighted MR method showed that genetically-increased risk of poor oral health was associated with a higher risk of ICH (OR 2.34, [1.08-5.06], p=0.029). Secondary analyses indicated a more potent association with deep ICH (OR 3.20 [1.34-7.6], p=0.008), whereas the link with lobar ICH was not statistically significant (OR 1.32 [0.53-3.27], p=0.543). Sensitivity analyses detected no horizontal pleiotropy in our findings (MR-PRESSO global test p-values &gt;0.05). Conclusion: Genetically-determined poor oral health is associated with an increased risk of ICH, particularly in the case of deep ICH. Because gene-disease associations are less prone to confounding, our results suggest that this association is causal. However, further analyses are needed to validate these results and identify the mediating mechanisms. Because oral health is an easily modifiable process, it may be a promising target for very early interventions focused on mitigating the risk of hemorrhagic stroke.

Genetically predicted causality between gut microbiota, blood metabolites, and intracerebral hemorrhage: a bidirectional Mendelian randomization study.

Recent research linked changes in the gut microbiota and serum metabolite concentrations to intracerebral hemorrhage (ICH). However, the potential causal relationship remained unclear. Therefore, the current study aims to estimate the effects of genetically predicted causality between gut microbiota, serum metabolites, and ICH. Summary data from genome-wide association studies (GWAS) of gut microbiota, serum metabolites, and ICH were obtained separately. Gut microbiota GWAS (N = 18,340) were acquired from the MiBioGen study, serum metabolites GWAS (N = 7,824) from the TwinsUK and KORA studies, and GWAS summary-level data for ICH from the FinnGen R9 (ICH, 3,749 cases; 339,914 controls). A two-sample Mendelian randomization (MR) study was conducted to explore the causal effects between gut microbiota, serum metabolites, and ICH. The random-effects inverse variance-weighted (IVW) MR analyses were performed as the primary results, together with a series of sensitivity analyses to assess the robustness of the results. Besides, a reverse MR was conducted to evaluate the possibility of reverse causation. To validate the relevant findings, we further selected data from the UK Biobank for analysis. MR analysis results revealed a nominal association (p < 0.05) between 17 gut microbial taxa, 31 serum metabolites, and ICH. Among gut microbiota, the higher level of genus Eubacterium xylanophilum (odds ratio (OR): 1.327, 95% confidence interval (CI):1.154-1.526; Bonferroni-corrected p = 7.28 × 10-5) retained a strong causal relationship with a higher risk of ICH after the Bonferroni corrected test. Concurrently, the genus Senegalimassilia (OR: 0.843, 95% CI: 0.778-0.915; Bonferroni-corrected p = 4.10 × 10-5) was associated with lower ICH risk. Moreover, after Bonferroni correction, only two serum metabolites remained out of the initial 31 serum metabolites. One of the serum metabolites, Isovalerate (OR: 7.130, 95% CI: 2.648-19.199; Bonferroni-corrected p = 1.01 × 10-4) showed a very strong causal relationship with a higher risk of ICH, whereas the other metabolite was unidentified and excluded from further analysis. Various sensitivity analyses yielded similar results, with no heterogeneity or directional pleiotropy observed. This two-sample MR study revealed the significant influence of gut microbiota and serum metabolites on the risk of ICH. The specific bacterial taxa and metabolites engaged in ICH development were identified. Further research is required in the future to delve deeper into the mechanisms behind these findings.

Abstract 9398: Associations Between Blood Pressure, Race/Ethnicity, and Incident Stroke Type: A Pooled Cohort Analysis of ARIC, CARDIA, CHS, MESA, FOS, NOMAS

Introduction: Stroke risk varies by systolic blood pressure (SBP) and race/ethnicity. Whether the relationship between cumulative mean SBP and first-time incident stroke type differs by racial/ethnic group is unknown. This study examines the relationship between cumulative mean SBP and first-time incident stroke among 3 major stroke types: ischemic stroke (IS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) and how race/ethnicity influences these relationships, using a pooled cohort analysis. Hypothesis: We hypothesize that race/ethnicity modifies the association between cumulative mean SBP and incident stroke type. Methods: Data were pooled from 38,325 participants with baseline age ≥18 and ≥1 SBP measurement before the first incident stroke from 6 US longitudinal cohorts from 1971 to 2019: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study. A multivariable-adjusted Cox proportional hazard model was used to estimate the association between cumulative mean SBP, race/ethnicity, and time to incident stroke (overall, stroke type, and race/ethnicity*stroke type). Results: Median follow-up was 22.3 years. Mean (SD) baseline age was 53.2 (17.1) years, with 54.5% female, 24.9% Black, and 8.8% Hispanic. Baseline mean (SD) SBP was 136.8 (20.5) mmHg. Race/ethnicity modified the association of SBP with time to ICH (P-interaction=0.006) but no other stroke types. Compared to White participants, the association between higher SBP on ICH risk was greater in Black participants but not different in Hispanic participants (Table). A 10-mmHg higher SBP was associated with a higher risk of ICH than IS (Table). Conclusions: We found that race modifies the association between SBP and ICH risk, such that ICH risk is 19% higher per 10-mmHg for Black individuals than White individuals.

Symptomatic intracerebral hemorrhage after non-emergency percutaneous coronary intervention: Incidence, risk factors, and association with cardiovascular outcomes.

ObjectiveTo investigate the incidence, risk factors, and association with cardiovascular outcomes of patients who developed symptomatic intracerebral hemorrhage (ICH) after non-emergency percutaneous coronary intervention (PCI).MethodsWe conducted a single-institution retrospective study of patients who developed symptomatic ICH after non-emergency PCI. To identify associations between clinical variables and outcomes, Cox-proportional hazards regression models were constructed. Outcomes analyzed include (1) all-cause mortality, (2) acute ischemic stroke (AIS) or transient ischemic attack (TIA), and (3) major adverse cardiovascular events (MACE).ResultsA total of 1,732 patients were included in the analysis. The mean (±SD) age was 61.1 (±11.3) years, and 1,396 patients (80.6%) were male. The cumulative incidence of symptomatic ICH after non-emergency PCI was 1.3% (22 patients). Age, chronic kidney disease, and prior coronary artery bypass graft surgery were independently associated with a higher risk of ICH after PCI, while hyperlipidemia was independently associated with a lower risk of ICH after PCI. ICH after PCI was independently associated with a higher risk of all-cause mortality and AIS or TIA after PCI.ConclusionPatients who are older, who have chronic kidney disease, and who have had prior coronary artery bypass graft surgery should be monitored for symptomatic ICH after non-emergency PCI.

Association of Chronic Kidney Disease With Risk of Intracerebral Hemorrhage

The evidence linking chronic kidney disease (CKD) to spontaneous intracerebral hemorrhage (ICH) is inconclusive owing to possible confounding by comorbidities that frequently coexist in patients with these 2 diseases. To determine whether there is an association between CKD and ICH risk. A 3-stage study that combined observational and genetic analyses was conducted. First, the association between CKD and ICH risk was tested in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a multicenter case-control study in the US. All participants with available data on CKD from ERICH were included. Second, this analysis was replicated in the UK Biobank (UKB), an ongoing population study in the UK. All participants in the UKB were included in this study. Third, mendelian randomization analyses were implemented in the UKB using 27 CKD-related genetic variants to test for genetic associations. ERICH was conducted from August 1, 2010, to August 1, 2017, and observed participants for 1 year. The UKB enrolled participants between 2006 and 2010 and will continue to observe them for 30 years. Data analysis was performed from November 11, 2019, to May 10, 2022. CKD stages 1 to 5. The outcome of interest was ICH, ascertained in ERICH via expert review of neuroimages and in the UKB via a combination of self-reported data and International Statistical Classification of Diseases, Tenth Revision, codes. In the ERICH study, a total of 2914 participants with ICH and 2954 controls who had available data on CKD were evaluated (mean [SD] age, 61.6 [14.0] years; 2433 female participants [41.5%]; 3435 male participants [58.5%]); CKD was found to be independently associated with higher risk of ICH (odds ratio [OR], 1.95; 95% CI, 1.35-2.89; P < .001). This association was not modified by race and ethnicity. Replication in the UKB with 1341 participants with ICH and 501 195 controls (mean [SD] age, 56.5 [8.1] years; 273 402 female participants [54.4%]; 229 134 male participants [45.6%]) confirmed this association (OR, 1.28; 95% CI, 1.01-1.62; P = .04). Mendelian randomization analyses indicated that genetically determined CKD was associated with ICH risk (OR, 1.56; 95% CI, 1.13-2.16; P = .007). In this 3-stage study that combined observational and genetic analyses among study participants enrolled in 2 large observational studies with different characteristics and study designs, CKD was consistently associated with higher risk of ICH. Mendelian randomization analyses suggest that this association was causal. Further studies are needed to identify the specific biological pathways that mediate this association.

Genetically-Proxied Levels of Vitamin D and Risk of Intracerebral Hemorrhage.

BackgroundThe evidence linking vitamin D (VitD) levels and spontaneous intracerebral hemorrhage (ICH) remains inconclusive. We tested the hypothesis that lower genetically determined VitD levels are associated with higher risk of ICH.Methods and ResultsWe conducted a 2 sample Mendelian Randomization (MR) study using publicly available summary statistics from published genome‐wide association studies of VitD levels (417 580 study participants) and ICH (1545 ICH cases and 1481 matched controls). We used the inverse‐variance weighted approach to generate causal estimates and the MR Pleiotropy Residual Sum and Outlier and MR‐Egger approaches to assess for horizontal pleiotropy. To account for known differences in their underlying mechanism, we implemented stratified analysis based on the location of the hemorrhage within the brain (lobar or nonlobar). Our primary analysis indicated that each SD decrease in genetically instrumented VitD levels was associated with a 60% increased risk of ICH (odds ratio [OR], 1.60; [95% CI, 1.05–2.43]; P=0.029). We found no evidence of horizontal pleiotropy (MR‐Egger intercept and MR Pleiotropy Residual Sum and Outlier global test with P>0.05). Stratified analyses indicated that the association was stronger for nonlobar ICH (OR, 1.87; [95% CI, 1.18–2.97]; P=0.007) compared with lobar ICH (OR, 1.43; [95% CI, 0.86–2.38]; P=0.17).ConclusionsLower levels of genetically proxied VitD levels are associated with higher ICH risk. These results provide evidence for a causal role of VitD metabolism in ICH.

The Association between Low Levels of Low Density Lipoprotein Cholesterol and Intracerebral Hemorrhage: Cause for Concern?

Excessive levels of low-density lipoprotein cholesterol (LDL-C) in the blood are a known risk factor for atherosclerosis, and a common target of treatment for primary and secondary prevention of cerebrocardiovascular disease. As lipid lowering agents including statins, ezetimibe and anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have shown good therapeutic results, the guidelines are constantly lowering the “optimal” LDL-C goals. However, old and new data point towards an association between low LDL-C and total cholesterol and intracerebral hemorrhage (ICH). In this review we aimed to shed light on this troubling association and identify the potential risk factors of such a potential adverse reaction. With respect to the data presented, we concluded that in patients with high risk of ICH, a cautious approach and individualized therapy strategy are advised when considering aggressive LDL reduction.

Congenital Coagulation Factor XIII Deficiency Revealed by Convulsion: A Case Report

Factor XIII deficiency is a rare inherited disease, with a particularly high risk of intracerebral hemorrhage. We report the case of a newborn who was suspected to have a coagulation disorder at birth, due to an intracerebral hemorrhage. A quantitative dosage of factor XIII was requested but the usual coagulation tests (thromboplastin, thrombokinase, fibrinogen) were normal. Because of unavailability of specific treatment with factor XIII concentrate, the patient was treated with fresh frozen plasma. The initial dose was for normalizing factor XIII; subsequent monthly doses were designed for preventing the occurrence of serious bleeding.

Fibrinogen depletion and intracerebral hemorrhage after thrombolysis for ischemic stroke: a meta-analysis.

Intracerebral hemorrhage (ICH) can be a fatal complication of intravenous thrombolysis (IVT) for acute ischemic stroke. An early coagulopathy can develop after IVT, in relation to a significant fibrinogen depletion, increasing the risk of ICH. This systematic review and meta-analysis aimed at defining the role of fibrinogen depletion after IVT on the risk of ICH after IVT. Protocol was registered with PROSPERO (CRD42020124241) and followed PRISMA and MOOSE guidelines. We systematically searched English studies reporting rates of post-IVT ICH depending on fibrinogen depletion until 7/1/2021. Primary outcome was symptomatic ICH (sICH). Meta-analysis followed random-effects model to account for heterogeneity in design and timing of ascertainments. Biases were assessed via the Newcastle-Ottawa Scale. Overall, among 352 records identified, 5 observational studies were eligible for quantitative synthesis (n = 2142), all of fair quality. Considering sICH within 24-36h post-IVT, pooling data from 4 studies (n = 1753), fibrinogen depletion consistently increased the risk of sICH (OR 3.67, 95%CI 2.28-5.90, pheterogeneity = 0.55). Pooling adjusted estimated for age, gender, and NIHSS from 3 studies (n = 723), fibrinogen depletion was confirmed to significantly increase the risk of ICH after IVT (OR 5.41, 95%CI 2.96-9.89). Fibrinogen depletion significantly increases the risk of ICH after IVT for acute ischemic stroke. Routine fibrinogen assessment might be considered to identify people at higher risk of ICH. As fibrinogen repletion is feasible, trials should investigate its efficacy in preventing ICH, potentially increasing the net benefit profile of IVT in acute ischemic stroke.

Endovascular Treatment of Infective Endocarditis-Related Acute Large Vessel Occlusion Stroke

ObjectivesEmbolic stroke is a frequent complication of infective endocarditis yet lacks acute treatment as intravenous thrombolysis should be avoided due to high risk of intracerebral hemorrhage. Mechanical thrombectomy for large vessel occlusion may be a promising treatment but there is limited data on safety outcomes in infective endocarditis. Materials and methodsIn this multi-center retrospective case series, we reviewed data from patients with infective endocarditis-related large vessel occlusion who underwent mechanical thrombectomy in 9 US hospitals. ResultsWe identified 15 patients at 9 hospitals. A minority presented with signs suggesting infection (2 patients (14%) had fever, 7 (47%) were tachycardic, 2 (13%) were hypotensive, and 8 (53%) had leukocytosis). The median National Institute of Health Stroke Score decreased from 19 (range 9-25) at presentation to 7 post-thrombectomy (range 0-22, median best score post-thrombectomy), and the median modified Rankin Scale on or after discharge for survivors was 3 (range 0-6). Approximately 57% of patients had a modified Rankin Scale between 0 and 3 on or after discharge. Hemorrhagic transformation was observed in 7/15 (47%). The mechanical thrombectomy group had 2/9 petechial hemorrhagic transformation (22%), compared to 4/6 parenchymal hematomas (67%) in the tissue plasminogen activator + mechanical thrombectomy group. ConclusionsOur findings suggest that patients with large vessel occlusion due to infective endocarditis may not present with overt signs of infection. Mechanical thrombectomy may be an effective treatment in this patient population for whom intravenous thrombolysis should be avoided.

Systemic arterial blood pressure and intracerebral hemorrhage after mechanical thrombectomy in anterior cerebral circulation

The relationship between systemic arterial blood pressure (BP) and intracerebral hemorrhage (ICH) after mechanical thrombectomy (MT) of the cerebral artery remains unclear. This study aimed to determine the effect of...

Abstract P696: Organic Sleep Disorders Are Linked With Stroke- A Nationwide Population Study

Objective: Primary aim of this study is to identify prevalence of organic sleep disorders (OSDs) [REM sleep behaviour disorder (REMSBD), hypersomnia, parasomonia, insomnia, circadian rhythm] and compare prevalence of stroke [acute ischemic stroke (AIS), transient ischemic attack (TIA), intracerebral hemorrhage (ICeH), subarachnoid hemorrhage (SAH)] amongst OSDs. Secondary aim of the study is to evaluate the association between OSDs and stroke subtypes. Methods: A retrospective study was performed using National Inpatient Sample [2016-2017] for adult hospitalizations. We extracted a cohort of diagnoses of OSDs amongst which diagnoses of stroke were identified using ICD 10 code. Weighted analysis using chi-square test and mix-effects multivariable survey logistic regression was performed to evaluate the prevalence and odds of stroke amongst OSDs. Results: Out of 58,259,589 US hospitalizations, 2715 (0.00005%), 4120 (0.01%), 3420 (0.01%), 1,301,209 (2.23%) and 24870 (0.04%) had REMSBD, parasomnia, circadian rhythm, insomnia, and hypersomnia, respectively. Prevalence of AIS was higher in REMSBD [3.1 vs 2.1% p&lt;.0004], hypersomnia [2.7 vs 2.1% p&lt;.0001], parasomnia [2.6 vs 2.1% p=.0714], and circadian rhythm [2.8 vs 2.1% p=.0102]. Prevalence of TIA was higher in REMSBD [1.3 vs 0.6% p&lt;.0001], parasomnia [1.3 vs 0.6% p&lt;.0001] and hypersomnia [0.7 vs 0.5% p=.0188]. Prevalence of ICeH was higher in hypersomnia [0.5 vs 0.4% p=.0043], parasomnia [0.5 vs 0.4% p=.3239], and circadian rhythm [1.3 vs 0.4% p=.0188]. Prevalence of SAH was higher in circadian rhythm [0.6 vs 0.1% p&lt;.0001]. In analysis, patients with parasomnia had higher odds of TIA [aOR 2.8; 95%CI 1.02-7.5] and a weak association with ICeH [1.9 (0.5-7.9)]. Circadian rhythm OSD had 214% [3.1 (1.6-6.1)] and 310% [4.1 (1.5-11.0)] higher risk of ICeH and SAH, respectively and a weak association with AIS [1.3 (0.8-2.1)]. Hypersomnia had a weak association with AIS [1.2 (1.0-1.4)], TIA [1.1 (0.8-1.6)] and ICeH [1.4 (0.9-2.0)]. REMSBD had a weak association with AIS [3.6 (0.8-15.4)]. Conclusion: Our study shows organic sleep disorders (OSDs) are associated with strokes. Even Though the extent of association varies in each OSDs, early identification and prompt management of OSDs may mitigate the risk of stroke.

Recurrent Stroke Incidence and Etiology in Patients with Embolic Stroke of Undetermined Source and Other Stroke Subtypes.

Aims: This study aimed at clarifying the incidence of recurrent stroke and its etiology in patients with embolic stroke of undetermined source (ESUS) and other stroke subtypes in both the acute and chronic periods. Methods: A total of 645 patients who were admitted with acute ischemic stroke (IS) between March 2015 and August 2019 were enrolled. Among them, 511 patients with ESUS, cardioembolism (CE), large artery atherosclerosis (LAA), or small vessel disease (SVD) were analyzed in this study. After discharge, 391 patients who visited the outpatient clinic were followed up until August 2020. The outcome was stroke recurrence. Results: In the acute admission, recurrence rates were 7.6%, 8.1%, 18.8%, and 2.2% in patients with ESUS, CE, LAA, and SVD, respectively, and there were significant differences between the groups. The subtype of recurrence was almost identical to that of the index stroke. In the outpatient clinic, the annual recurrence rates were 4.4%, 4.3%, 6.0%, and 2.9% in ESUS, CE, LAA, and SVD, respectively, and no difference was observed. Subtypes of recurrence in outpatients with ESUS included ESUS, intracerebral hemorrhage (ICH), and SVD. Patients with ESUS and SVD had a higher risk of ICH during follow-up. Conclusions: Although the risk of recurrence was comparable between patients with ESUS and CE and intermediate between patients with LAA and SVD, in the acute admission unit, the risk in outpatients was similar among all subtypes. ESUS was the most recurrent stroke subtype in outpatients with ESUS. The risk of hemorrhagic stroke was significant in patients with SVD and ESUS.

Nationwide Patterns of Hemorrhagic Stroke among Patients Hospitalized with Brain Metastases: Influence of Primary Cancer Diagnosis and Anticoagulation

Brain metastases can contribute to a decreased quality of life for patients with cancer, often leading to malaise, neurologic dysfunction, or death. Intracerebral hemorrhage (ICH) is an especially feared complication in patients with brain metastases given the potential for significant morbidity and mortality. We aim to characterize patients with cancer and brain metastases admitted to hospitals nationwide and identify factors associated with ICH. The 2016 Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) was queried for all patients with cancer hospitalized with a diagnosis of brain metastases. Admissions with a primary or secondary diagnosis of ICH were further identified. Baseline differences in demographic, clinical, socioeconomic, and hospital-related characteristics between patients with and without ICH were assessed by chi-square, Mann-Whitney U, and ANOVA testing. Multivariable logistic regression was used to identify factors associated with ICH. Weighted frequencies were used to create national estimates for all data analysis. In 2016, a total 145,225 hospitalizations were associated with brain metastases, of which 4,145 (2.85%) had a concurrent diagnosis of ICH. Patients with ICH were more likely to have a longer length of stay (median 5 days vs 4 days, p<0.001) and a higher cost of stay (median $14241.14 vs $10472.54, p<0.001). ICH was found to be positively associated with having a diagnosis of melanoma (odds ratio [OR] 5.01; 95% Confidence Interval [CI] 3.50-7.61) and kidney cancer (OR 2.50; 95% CI 1.69-3.72). Patients on long-term anticoagulation had a higher risk of ICH (OR 1.49; CI 1.15-1.91). Approximately 3% of patients hospitalized with brain metastasis also had a diagnosis of ICH, which was significantly associated with longer length of stay and cost. Patients with melanoma, kidney cancer, and on long-term anticoagulation had a higher risk of ICH. Physicians should consider the risks of anticoagulation carefully for patients with brain metastasis, especially those with melanoma and kidney cancer.

Nationwide Patterns of Hemorrhagic Stroke among Patients Hospitalized with Brain Metastases: Influence of Primary Cancer Diagnosis and Anticoagulation

Brain metastases can contribute to a decreased quality of life for patients with cancer, often leading to malaise, neurologic dysfunction, or death. Intracerebral hemorrhage (ICH) is especially feared complication in patients with brain metastases given the potential for significant morbidity and mortality. We aim to characterize patients with cancer and brain metastases admitted to hospitals nationwide and identify factors associated with ICH. The 2016 Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) was queried for all patients with cancer hospitalized with a diagnosis of brain metastases. Admissions with a primary or secondary diagnosis of ICH were further identified. Baseline differences in demographic, clinical, socioeconomic, and hospital-related characteristics between patients with and without ICH were assessed by chi-square, Mann-Whitney U, and ANOVA testing. Multivariable logistic regression was used to identify factors associated with ICH. Weighted frequencies were used to create national estimates for all data analysis. In 2016, a total 145,225 hospitalizations were associated with brain metastases, of which 4,145 (2.85%) had a concurrent diagnosis of ICH. Patients with ICH were more likely to have a longer length of stay (median 5 days vs 4 days, p < 0.001) and a higher cost of stay (median $14241.14 vs $10472.54, p < 0.001). ICH was found to be positively associated with having a diagnosis of melanoma (odds ratio [OR] 5.01; 95% Confidence Interval [CI] 3.50-7.61) and kidney cancer (OR 2.50; 95% CI 1.69-3.72). Patients on long-term anticoagulation had a higher risk of ICH (OR 1.49; CI 1.15-1.91). Approximately 3% of patients hospitalized with brain metastasis also had a diagnosis of ICH, which was significantly associated with longer length of stay and cost. Patients with melanoma, kidney cancer, and on long-term anticoagulation had a higher risk of ICH. Physicians should consider the risks of anticoagulation carefully for patients with brain metastasis, especially those with melanoma and kidney cancer.

Sleep Duration and Stroke: Prospective Cohort Study and Mendelian Randomization Analysis.

Studies of sleep duration in relation to specific types of stroke are scarce. Moreover, the results are inconclusive and causality remains unclear. Our objective was to investigate whether sleep duration is associated with risk of stroke and its types using observational and Mendelian randomization designs. The prospective study included 79 881 women and men (45-79 years of age) who were followed up for incident stroke or death over a mean follow-up of 14.6 years (1 164 646 person-years) through linkage to Swedish Registers. For the Mendelian randomization study, single-nucleotide polymorphisms associated with sleep duration were identified from a genome-wide association study. Summarized data for genetic associations with stroke were obtained from publicly available data of the MEGASTROKE and the International Stroke Genetics Consortia. Compared with normal sleep duration, long sleep (≥9 hours per day) was associated with increased risk of total and ischemic stroke (hazard ratios [95% CI], 1.12 [1.03-1.22] and 1.14 [1.03-1.24], respectively), whereas short sleep (<7 h/d) was linked to higher risk of intracerebral hemorrhage (hazard ratio [95% CI], 1.21 [1.03-1.41]). The 2-sample Mendelian randomization analysis supported no causal association of short or long sleep duration with ischemic stroke as a whole. In a prospective study, long sleep duration was associated with increased risk of total and ischemic stroke, whereas short sleep was linked to increased risk of intracerebral hemorrhage. However, the Mendelian randomization analysis did not show a significant detrimental effect of short or long sleep duration on the risk of total stroke or stroke types.

Reader response: Low-density lipoprotein cholesterol and risk of intracerebral hemorrhage: A prospective study.

Ma et al.1 performed a prospective study to evaluate the association between the low-density lipoprotein cholesterol (LDL-C) level and intracerebral hemorrhage (ICH) risk. The results suggested that a significant association between lower LDL-C and higher risk of ICH was observed when LDL-C was <70 mg/dL.