Outcomes of newly diagnosed atrial fibrillation in patients with acute coronary syndromes.

BACKGROUND: Acute coronary syndrome (ACS) is frequently accompanied by newly diagnosed atrial fibrillation (AF). AIMS: We aimed to compare the risk of major adverse cardiovascular events (MACE) in ACS patients presenting with known, newly diagnosed, or no AF. METHODS: In our multicentre, prospective registry study, we included patients with confirmed ACS. Patients are classified as having known, newly diagnosed or no AF. Newly diagnosed AF is subdivided according to the duration of the episode, time of onset, post-coronary artery bypass graft (CABG) or spontaneous occurrence, and treatment with oral anticoagulants (OAC). The primary endpoint is MACE at 1 year. Key secondary endpoints include ischaemic stroke and bleeding complications. RESULTS: Amongst 4,433 patients with confirmed ACS, 3,598 (81.2%) had no AF, 438 (9.9%) had newly diagnosed AF, and 397 (9.0%) had known AF. The rates of OAC treatment at discharge were 53.4% in patients with newly diagnosed AF and 89.2% in patients with known AF. After adjusting for baseline imbalances, only new AF was independently associated with increased rates of MACE, whereas known AF was not (hazard ratio [HR] 1.52, 95% confidence interval [CI]: 1.19-1.90 and HR 0.93, 95% CI: 0.70-1.23). For ACS patients with newly diagnosed AF, episodes lasting >24 hours were associated with a higher risk of MACE compared to episodes <24 hours (HR 1.99, 95% CI: 1.36-2.93). Episodes of new AF occurring post-CABG had more favourable outcomes compared to spontaneously occurring new AF (HR for MACE 0.52, 95% CI: 0.31-0.86). OAC treatment rates were higher in the new AF subcategories with higher rates of MACE and ischaemic stroke. CONCLUSIONS: Newly diagnosed AF in ACS patients was associated with higher rates of MACE and ischaemic stroke compared to ACS patients without or with known AF. Among the ACS patients with new AF, an episode lasting >24 hours was associated with worse outcomes than shorter episodes, while post-CABG occurrence of AF showed relatively better outcomes compared to spontaneously occurring AF. Only 53% of new AF patients were discharged on OAC therapy versus 89% with known AF.

The incidence and risk factors of perioperative recurrent stroke in elderly patients with previous ischemic stroke receiving hip fracture surgery.

BACKGROUND: Data are currently lacking regarding perioperative stroke recurrence in hip fracture patients with previous stroke. We aimed to analyze the incidence and risk factors of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery. METHODS: We used 2019 and 2020 data from the United States National Inpatient Sample database. We identified elderly patients with previous ischemic stroke who had undergone hip fracture surgery to analyze the incidence of stroke recurrence. A 1:4 propensity score matching was used to balance confounding factors related to demographic data and matched the control group with the stroke recurrence group. Risk factors for stroke recurrence were determined using univariate and multivariate logistic analysis. RESULTS: The incidence of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery was 5.7% (51/882). Multivariate logistic regression analysis showed that intertrochanteric fracture (odds ratio 2.24, 95% confidence interval 1.14-4.57; p = 0.021), hypertension (odds ratio 2.49, 95% confidence interval 1.26-5.02; p = 0.009), and postoperative pneumonia (odds ratio 4.35, 95% confidence interval 1.59-11.82; p = 0.004) were independently associated with stroke recurrence. CONCLUSIONS: The perioperative stroke recurrence rate in elderly hip fracture patients with previous stroke was 5.7%. Intertrochanteric fracture, hypertension, and postoperative pneumonia were identified as factors significantly associated with stroke recurrence in this study. Adequate systemic support post-fracture, effective blood pressure management, and proactive infection prevention may help reduce stroke recurrence, especially in patients with intertrochanteric fractures.

Healthy Lifestyles Modify the Association of Melatonin Receptor 1B Gene and Ischemic Stroke: A Family-Based Cohort Study in Northern China.

Limited research has reported the association between MTNR1B gene polymorphisms and ischemic stroke (IS), and there is insufficient evidence on whether adopting a healthy lifestyle can mitigate genetic risks in this context. This study aimed to investigate the associations between MTNR1B gene variants (rs10830963 and rs1387153) and IS, examining the potential effect of gene-lifestyle interactions on IS risk. Conducted in northern China, this family-based cohort study involved 5116 initially IS-free subjects. Genotype data for rs10830963 and rs1387153 in MTNR1B were collected. Eight modifiable lifestyle factors, including body mass index (BMI), smoking, alcohol consumption, dietary habits, physical activity, sedentary time, sleep duration, and chronotype, were considered in calculating healthy lifestyle scores. Multilevel Cox models were used to examine the associations between MTNR1B variants and IS. Participants carrying the rs10830963-G and rs1387153-T alleles exhibited an elevated IS risk. Each additional rs10830963-G allele and rs1387153-T allele increased the IS risk by 36% (HR = 1.36, 95% CI, 1.12-1.65) and 32% (HR = 1.32, 95% CI, 1.09-1.60), respectively. Participants were stratified into low, medium, and high healthy lifestyle score groups (1537, 2188, and 1391 participants, respectively). Genetic-lifestyle interactions were observed for rs10830963 and rs1387153 (p for interaction < 0.001). Notably, as the healthy lifestyle score increased, the effect of MTNR1B gene variants on IS risk diminished (p for trend < 0.001). This study underscores the association between the MTNR1B gene and IS, emphasizing that adherence to a healthy lifestyle can mitigate the genetic predisposition to IS.

Evaluation of demographic/clinical features and hemorrhagic complications in patients with ischemic stroke who underwent reperfusion therapy.

The relationship between demographic/clinical characteristics, clinical outcomes and the development of hemorrhagic complications in patients with ischemic stroke who underwent reperfusion therapy has not been studied sufficiently. We have aimed to compare genders and age groups in terms of clinical features and outcome; and types of reperfusion treatments and clinical features regarding the development of hemorrhagic complications in patients with ischemic stroke who underwent recombinant tissue plasminogen activator (rtPA) and/or thrombectomy. Patients with acute ischemic stroke undergoing rtPA and/or thrombectomy were divided into six age groups. Parameters including hemorrhagic complications, anticoagulant and antiaggregant use, hyperlipidemia, smoking status, biochemical parameters, and comorbidities were documented. National Institutes of Health Stroke Scale (NIHSS) scores, modified Rankin Score (mRS) and Glasgow Coma Scale scores were recorded. Etiological classification of stroke was done. These parameters were compared in terms of age groups, genders, and hemorrhagic complications. Significant differences were found between age groups concerning hypertension, coronary artery disease, smoking status, and antiaggregant use. Rate of hemorrhagic complications in rtPA group was significantly lower when compared with other treatment groups. Hemorrhagic complications developed mostly in the rtPA+thrombectomy group. Among the patients who developed hemorrhagic complications, NIHSS scores on admission were found to be significantly lower in men than women. Admission, discharge, and 3rd month mRS values in men were significantly lower than those of women. Knowing demographic and clinical features of patients that may have an impact on the clinical course of ischemic stroke managed with reperfusion therapy will be useful in predicting the hemorrhagic complications and clinical outcomes.

Long-term risk factors of recurrent stroke, myocardial infarction and death in patients leaving hospital with a diagnosis of ischemic stroke or TIA.

Objectives. The prevalence of patients with prior stroke is increasing globally. Accordingly, there is a need for up-to-date evidence of patient-related prognostic factors for stroke recurrence, post stroke myocardial infarction (MI) and death based on long-term follow-up of stroke survivors. For this purpose, the RIALTO study was established in 2004. Design. A prospective cohort study in which patients diagnosed with ischemic stroke (IS) or transient ischemic attack (TIA) in three Copenhagen hospitals were included. Data were collected from medical records and by structured interview. Data on first stroke recurrence, first MI and all-cause death were extracted from the Danish National Patient Registry and the Danish Civil Registration System. Results. We included 1215 patients discharged after IS or TIA who were followed up by register data from April 2004 to end of 2018 giving a median follow-up of 3.5-6.9 years depending on the outcome. At the end of follow-up 406 (33%) patients had been admitted with a recurrent stroke, 100 (8%) had a MI and 822 (68%) had died. Long-term prognostic predictors included body mass index, diabetes, antihypertensive and lipid lowering treatment, smoking, a sedentary lifestyle as well as poor self-rated health and psychosocial problems. Conclusions. Long-term risk of recurrent stroke and MI remain high in patients discharged with IS or TIA despite substantial improvements in tertiary preventive care in recent decades. Continued attention to the patient risk profile among patients surviving the early phase of stroke, including comorbidities, lifestyle, and psychosocial challenges, is warranted.

Association of Acute Incidental Cerebral Microinfarcts With Subsequent Ischemic Stroke in Patients With Cancer: A Population-Based Study.

BACKGROUND AND OBJECTIVES: Incidental diffuse-weighted imaging (DWI)-positive subcortical and cortical lesions, or acute incidental cerebral microinfarcts (CMIs), are a common type of brain ischemia, which can be detected on magnetic resonance DWI for approximately 2 weeks after occurrence. Acute incidental CMI was found to be more common in patients with cancer. Whether acute incidental CMI predicts future ischemic stroke is still unknown. We aimed to examine the association between acute incidental CMI in patients with cancer and subsequent ischemic stroke or transient ischemic attack (TIA). METHODS: This is a retrospective cohort study. We used Clalit Health Services records, representing over half of the Israeli population, to identify adults with lung, breast, pancreatic, or colon cancer who underwent brain MRI between January 2014 and April 2020. We included patients who underwent scan between 1 year before cancer diagnosis and 1 year after diagnosis. Primary outcome was ischemic stroke or TIA using International Classification of Diseases, Ninth Revision codes. Secondary outcomes were intracranial hemorrhage (ICH) and mortality. Records were followed from first MRI until primary outcome, death, or end of follow-up (January 2023). Cox proportional hazards models were used to calculate hazard ratio (HR) for patients with and without acute incidental CMI, as a time-dependent covariate. RESULTS: The study cohort included 1,618 patients with cancer, among whom, 59 (3.6%) had acute incidental CMI on at least 1 brain MRI. The median (interquartile range) time from acute incidental CMI to stroke or TIA was 26 days (14-84). On multivariable analysis, patients with acute incidental CMI had a higher stroke or TIA risk (HR 2.97, 95% CI 1.08-8.18, p = 0.035) compared with their non-CMI counterparts. Acute incidental CMIs were also associated with mortality after multivariable analysis (HR 2.76, 95% CI 2.06-3.71, p < 0.001); no association with ICH was found. DISCUSSION: Acute incidental CMI on brain MRI in patients with active cancer is associated with an increased risk of near-future ischemic stroke or TIA and mortality. This finding might suggest that randomly detected acute incidental CMI in patients with cancer may guide primary cerebrovascular risk prevention and etiologic workup.

High body mass index is associated with elevated risk of perioperative ischemic stroke in patients who underwent noncardiac surgery: A retrospective cohort study.

BACKGROUND: Body mass index (BMI) serves as a global metric for assessing obesity and overall health status. However, the impact of BMI, treated as a continuous variable, on the risk of perioperative stroke remains poorly understood. This retrospective cohort study aimed to elucidate the association between BMI and the risk of perioperative ischemic stroke in patients undergoing non-cardiovascular surgery. METHODS: A cohort of 223,415 patients undergoing noncardiac surgery at the First Medical Center of Chinese PLA General Hospital between January 1, 2008 and August 31, 2019 was screened. Preoperative high BMI, defined as BMI >22.64 kg/m2, was the primary exposure, and the outcome of interest was the new diagnosis of perioperative ischemic stroke within 30 days post-surgery. Robust controls for patient and intraoperative factors were implemented to minimize residual confounding. Logistic regression and propensity score matching were employed, and patients were stratified into subgroups for further investigation. RESULTS: The overall incidence of perioperative ischemic stroke was 0.23% (n = 525) in the cohort. After adjusting for patient-related variables (OR 1.283; 95% CI, 1.04-1.594; p < 0.05), surgery-related variables (OR 1.484; 95% CI, 1.2-1.849; p < 0.001), and all confounding variables (OR 1.279; 95% CI, 1.025-1.607; p < 0.05), patients with BMI >22.64 kg/m2 exhibited a significantly increased risk of perioperative ischemic stroke. This association persisted in the propensity score matched cohort (OR 1.577; 95% CI, 1.203-2.073; p < 0.01). Subgroup analyses indicated that preoperative BMI >22.64 kg/m2 correlated with an elevated risk of perioperative ischemic stroke in female patients, those with coronary heart disease, peripheral vascular diseases, and individuals undergoing neurosurgery. CONCLUSION: We first identified BMI >22.64 kg/m2 as a substantial and independent risk factor for perioperative ischemic stroke in Chinese noncardiac surgery patients. Normal BMI may not suffice as a universal preventive standard. Instead, a more stringent perioperative weight management approach is recommended, particularly for specific subgroups such as female patients, those with coronary heart disease and peripheral vascular disease, and individuals scheduled for neurosurgery.

Asymptomatic Intracranial Artery Stenosis/Occlusion in Heterozygous Familial Hypercholesterolemia: Its Frequency and Implications for Cerebrovascular and Cardiovascular Events.

BACKGROUND: The atherogenic characteristics of heterozygous familial hypercholesterolemia (HeFH) increase the risk of premature atherosclerotic cardiovascular disease including not only coronary artery disease but ischemic stroke. Asymptomatic intracranial artery stenosis/occlusion (IASO) is a major cause of ischemic stroke, but it has not yet been fully characterized in patients with HeFH. METHODS AND RESULTS: This study analyzed 147 clinically diagnosed subjects with HeFH who underwent magnetic resonance imaging/magnetic resonance angiography imaging for evaluation of IASO (≥50% diameter stenosis). Major adverse cerebrovascular and cardiovascular events (cardiac death, ischemic stroke, and acute coronary syndrome) were compared in patients with HeFH with and without asymptomatic IASO. Asymptomatic IASO was observed in 13.6% of patients with HeFH. The untreated low-density lipoprotein cholesterol level (240±95 versus 244±75 mg/dL; P=0.67) did not differ between the 2 groups. Despite the use of lipid-lowering therapies (statin, P=0.71; high-intensity statin, P=0.81; ezetimibe, P=0.33; proprotein convertase subxilisin/kexin type 9 inhibitor, P=0.39; low-density lipoprotein apheresis, P=0.14), on-treatment low-density lipoprotein cholesterol level in patients with both HeFH and IASO was still suboptimally controlled (97±62 versus 105±50 mg/dL; P=0.17), accompanied by a higher triglyceride level (median, 109 versus 79 mg/dL; P=0.001). During the 12.4-year observational period (interquartile range, 6.2-24.6 years), asymptomatic IASO exhibited a 4.04-fold greater likelihood of experiencing a major adverse cardiovascular event (95% CI, 1.71-9.55; P=0.001) in patients with HeFH. This increased risk of a major adverse cardiovascular event was consistently observed in a multivariate Cox proportional hazards model adjusting clinical characteristics (hazard ratio, 4.32 [95% CI, 1.71-10.9]; P=0.002). CONCLUSIONS: A total of 13.6% of Japanese subjects with HeFH presented with asymptomatic IASO. Despite lipid-lowering therapies, patients with both HeFH and IASO more likely had elevated risk of cerebrovascular and cardiovascular events. Our findings highlight asymptomatic IASO as a phenotypic feature of HeFH-related atherosclerosis, which ultimately affects future outcomes.

Protein Identification for Stroke Progression via Mendelian Randomization in Million Veteran Program and UK Biobank.

BACKGROUND: Individuals who have experienced a stroke, or transient ischemic attack, face a heightened risk of future cardiovascular events. Identification of genetic and molecular risk factors for subsequent cardiovascular outcomes may identify effective therapeutic targets to improve prognosis after an incident stroke. METHODS: We performed genome-wide association studies for subsequent major adverse cardiovascular events (MACE; ncases=51 929; ncontrols=39 980) and subsequent arterial ischemic stroke (AIS; ncases=45 120; ncontrols=46 789) after the first incident stroke within the Million Veteran Program and UK Biobank. We then used genetic variants associated with proteins (protein quantitative trait loci) to determine the effect of 1463 plasma protein abundances on subsequent MACE using Mendelian randomization. RESULTS: Two variants were significantly associated with subsequent cardiovascular events: rs76472767 near gene RNF220 (odds ratio, 0.75 [95% CI, 0.64-0.85]; P=3.69×10-8) with subsequent AIS and rs13294166 near gene LINC01492 (odds ratio, 1.52 [95% CI, 1.37-1.67]; P=3.77×10-8) with subsequent MACE. Using Mendelian randomization, we identified 2 proteins with an effect on subsequent MACE after a stroke: CCL27 ([C-C motif chemokine 27], effect odds ratio, 0.77 [95% CI, 0.66-0.88]; adjusted P=0.05) and TNFRSF14 ([tumor necrosis factor receptor superfamily member 14], effect odds ratio, 1.42 [95% CI, 1.24-1.60]; adjusted P=0.006). These proteins are not associated with incident AIS and are implicated to have a role in inflammation. CONCLUSIONS: We found evidence that 2 proteins with little effect on incident stroke appear to influence subsequent MACE after incident AIS. These associations suggest that inflammation is a contributing factor to subsequent MACE outcomes after incident AIS and highlights potential novel targets.

Qualifying Event and Recurrence of Ischemic Stroke in Symptomatic Artery Occlusion: A Post Hoc Analysis of CMOSS.

BACKGROUND: The authors aimed to elucidate the relationship between latest ischemic event and the incidence of subsequent ischemic stroke in patients with symptomatic artery occlusion. METHODS AND RESULTS: We analyzed the association between qualifying event-the latest ischemic event (transient ischemic attack [TIA] or stroke)-and the incidence of ipsilateral ischemic stroke in patients with symptomatic artery occlusion treated with medical therapy alone in CMOSS (Carotid or Middle Cerebral Artery Occlusion Surgery Study). The incidence of CMOSS primary outcomes, including any stroke or death within 30 days after randomization or ipsilateral ischemic stroke between 30 days and 2 years, between the bypass surgical and medical groups, stratified by qualifying events, was also compared. Of the 165 patients treated with medical therapy alone, 75 had a TIA and 90 had a stroke as their qualifying event. The incidence of ipsilateral ischemic stroke did not significantly differ between patients with a TIA and those with a stroke as their qualifying event (13.3% versus 6.7%, P=0.17). In multivariate analysis, the qualifying event was not associated with the incidence of ipsilateral ischemic stroke. There were no significant differences in the CMOSS primary outcomes between the surgical and medical groups, regardless of the qualifying event being TIA (10.1% versus 12.2%, P=0.86) or stroke (6.7% versus 8.9%, P=0.55). CONCLUSIONS: Among patients with symptomatic artery occlusion and hemodynamic insufficiency, the risk of subsequent ipsilateral ischemic stroke does not appear to be lower in patients presenting with a TIA compared with those with a stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01758614.

The Tryptophan Index Is Associated with Risk of Ischemic Stroke: A Community-Based Nested Case-Control Study.

BACKGROUND: The relative availability of the essential amino acid tryptophan in the brain, as indicated by the tryptophan index, which is the ratio of tryptophan to its competing amino acids (CAAs) in circulation, has been related to major depression. However, it remains unknown whether tryptophan availability is involved in the pathogenesis of ischemic stroke. AIMS: We aimed to investigate the relationship between the tryptophan index and the risk of ischemic stroke. METHODS: We performed a nested case-control study within a community-based cohort in eastern China over the period 2013 to 2018. The analysis included 321 cases of ischemic stroke and 321 controls matched by sex and date of birth. The plasma levels of tryptophan and CAAs, including tyrosine, valine, phenylalanine, leucine, and isoleucine, were measured by ultra-high-performance liquid chromatography-tandem mass spectrometry. Conditional logistic regression analyses were employed to determine incidence rate ratios (IRRs) and their 95% confidence intervals (CIs). RESULTS: After adjustment for body mass index, current smoking status, educational attainment, physical activity, family history of stroke, hypertension, diabetes, hyperlipidemia, and estimated glomerular filtration rate, an elevated tryptophan index was significantly associated with a reduced risk of ischemic stroke in a dose-response manner (IRR, 0.76; 95% CI, 0.63-0.93, per standard deviation increment). The plasma tryptophan or CAAs were not separately associated with the risk of ischemic stroke. CONCLUSIONS: The tryptophan index was inversely associated with the risk of ischemic stroke. Our novel observations suggest that the availability of the essential amino acid tryptophan in the brain is involved in the pathogenesis of ischemic stroke.

Ischemic Stroke with Comorbid Cancer Has Specific miRNA-mRNA Networks in Blood That Vary by Ischemic Stroke Mechanism.

OBJECTIVE: Approximately half of ischemic strokes (IS) in cancer patients are cryptogenic, with many presumed cardioembolic. We evaluated whether there were specific miRNA and mRNA transcriptome architectures in peripheral blood of IS patients with and without comorbid cancer, and between cardioembolic versus noncardioembolic IS etiologies in comorbid cancer. METHODS: We studied patients with cancer and IS (CS; n = 42), stroke only (SO; n = 41), and cancer only (n = 28), and vascular risk factor-matched controls (n = 30). mRNA-Seq and miRNA-Seq data, analyzed with linear regression models, identified differentially expressed genes in CS versus SO and in cardioembolic versus noncardioembolic CS, and miRNA-mRNA regulatory pairs. Network-level analyses identified stroke etiology-specific responses in CS. RESULTS: A total of 2,085 mRNAs and 31 miRNAs were differentially expressed between CS and SO. In CS, 122 and 35 miRNA-mRNA regulatory pairs, and 5 and 3 coexpressed gene modules, were associated with cardioembolic and noncardioembolic CS, respectively. Complement, growth factor, and immune/inflammatory pathways showed differences between IS etiologies in CS. A 15-gene biomarker panel assembled from a derivation cohort (n = 50) correctly classified 81% of CS and 71% of SO participants in a validation cohort (n = 33). Another 15-gene panel correctly identified etiologies for 13 of 13 CS-cardioembolic and 11 of 11 CS-noncardioembolic participants upon cross-validation; 11 of 16 CS-cryptogenic participants were predicted cardioembolic. INTERPRETATION: We discovered unique mRNA and miRNA transcriptome architecture in CS and SO, and in CS with different IS etiologies. Cardioembolic and noncardioembolic etiologies in CS showed unique coexpression networks and potential master regulators. These may help distinguish CS from SO and identify IS etiology in cryptogenic CS patients. ANN NEUROL 2024;96:565-581.

Outcomes of Bypass Surgery in Adult Moyamoya Disease by Onset Type.

Importance: Moyamoya disease (MMD) is a rare chronic cerebrovascular disease, and the outcomes of bypass management in adult patients remain controversial. Objective: To categorize adult MMD based on asymptomatic, ischemic, and hemorrhagic onset and compare the outcomes (death, hemorrhagic stroke [HS], and ischemic stroke [IS]) of bypass surgery (direct or indirect) with those of conservative management. Design, Setting, and Participants: This retrospective, nationwide, population-based longitudinal cohort study used Korean National Health Insurance Research data to identify adults (aged ≥15 years) with MMD who were diagnosed between January 1, 2008, and December 31, 2020, and followed up until December 31, 2021 (median follow-up, 5.74 [IQR, 2.95-9.42] years). A total of 19 700 participants (3194 with hemorrhagic, 517 with ischemic, and 15 989 with asymptomatic MMD) were included. Data were analyzed from January 2 to April 1, 2023. Exposures: Bypass surgery and conservative management. Main Outcomes and Measures: Death constituted the primary outcome; secondary outcomes consisted of HS or IS. Kaplan-Meier survival curve and Cox proportional hazards regression analysis were applied. The propensity score-matching and stratified analyses were performed to control covariate effects. Results: A total of 19 700 patients (mean [SD] age, 45.43 [14.98] years; 12 766 [64.8%] female) were included. Compared with conservative management, bypass was associated with a reduced risk of death (adjusted hazard ratio [AHR], 0.50 [95% CI, 0.41-0.61]; P < .001) and HS (AHR, 0.36 [0.30-0.40]; P < .001) in hemorrhagic MMD; reduced risk of IS (AHR, 0.55 [95% CI, 0.37-0.81]; P = .002) in ischemic MMD; and reduced risk of death (AHR, 0.74 [95% CI, 0.66-0.84]; P < .001) in asymptomatic MMD. However, bypass was associated with an increased risk of HS (AHR, 1.76 [95% CI, 1.56-2.00]; P < .001) in asymptomatic MMD. Both direct and indirect bypass demonstrated similar effects in hemorrhagic and asymptomatic MMD, except only direct bypass was associated with a reduced risk of IS (AHR, 0.52 [95% CI, 0.33- 0.83]; P = .01) in ischemic MMD. After stratification, bypass was associated with a reduced risk of death in patients younger than 55 years with ischemic (AHR, 0.34 [95% CI, 0.13- 0.88]; P = .03) and asymptomatic (AHR, 0.69 [95% CI, 0.60-0.79]; P < .001) MMD, but an increased risk of HS in patients 55 years or older with ischemic MMD (AHR, 2.13 [95% CI, 1.1-4.16]; P = .03). Conclusions and Relevance: The findings of this cohort study of bypass outcomes for patients with MMD emphasize the importance of tailoring management strategies in adult patients based on onset types.

Incidence of recurrent ischemic stroke and its associated factors in a tertiary care center in Thailand: a retrospective cohort study.

BACKGROUND: Ischemic stroke (IS) is one of the leading causes of death among non-communicable diseases in Thailand. Patients who have survived an IS are at an increased risk of developing recurrent IS, which can result in worse outcomes and post-stroke complications. OBJECTIVES: The study aimed to investigate the incidence of recurrent IS among patients with first-ever IS during a one-year follow-up period and to determine its associated risk factors. METHODS: Adult patients (aged ≥ 18 years) who were hospitalized at the Stroke Center, King Chulalongkorn Memorial Hospital (KCMH) in Bangkok, Thailand, due to first-ever IS between January and December 2019 and had at least one follow-up visit during the one-year follow-up period were included in this retrospective cohort study. IS diagnosis was confirmed by neurologists and imaging. The log-rank test was used to determine the event-free survival probabilities of recurrent IS in each risk factor. RESULTS: Of 418 patients hospitalized due to first-ever IS in 2019, 366 (87.6%) were included in the analysis. During a total of 327.2 person-years of follow-up, 25 (6.8%) patients developed recurrent IS, accounting for an incidence rate of 7.7 per 100 person-year (95% confidence interval [CI] 5.2-11.3). The median (interquartile range) time of recurrence was 35 (16-73) days. None of the 47 patients with atrial fibrillation developed recurrent IS. The highest incidence rate of recurrent IS occurred within 1 month after the first episode (34 per 100 person-years) compared to other follow-up periods. Patients with small vessel occlusion and large-artery atherosclerosis (LAA) constituted the majority of patients in the recurrent IS episode (48% and 40%, respectively), with LAA exhibiting a higher recurrence rate (13.5%). Additionally, smoking status was found to be associated with an increased risk of recurrence. CONCLUSION: The incidence rate of the recurrence was moderate in our tertiary care setting, with a decreasing trend over time after the first episode. The various subtypes of IS and smoking status can lead to differences in event-free survival probabilities.

Risk Factors for Perinatal Arterial Ischemic Stroke: A Machine Learning Approach.

BACKGROUND AND OBJECTIVES: Perinatal arterial ischemic stroke (PAIS) is a focal vascular brain injury presumed to occur between the fetal period and the first 28 days of life. It is the leading cause of hemiparetic cerebral palsy. Multiple maternal, intrapartum, delivery, and fetal factors have been associated with PAIS, but studies are limited by modest sample sizes and complex interactions between factors. Machine learning approaches use large and complex data sets to enable unbiased identification of clinical predictors but have not yet been applied to PAIS. We combined large PAIS data sets and used machine learning methods to identify clinical PAIS factors and compare this data-driven approach with previously described literature-driven clinical prediction models. METHODS: Common data elements from 3 registries with patients with PAIS, the Alberta Perinatal Stroke Project, Canadian Cerebral Palsy Registry, International Pediatric Stroke Study, and a longitudinal cohort of healthy controls (Alberta Pregnancy Outcomes and Nutrition Study), were used to identify potential predictors of PAIS. Inclusion criteria were term birth and idiopathic PAIS (absence of primary causative medical condition). Data including maternal/pregnancy, intrapartum, and neonatal factors were collected between January 2003 and March 2020. Common data elements were entered into a validated random forest machine learning pipeline to identify the highest predictive features and develop a predictive model. Univariable analyses were completed post hoc to assess the relationship between each predictor and outcome. RESULTS: A machine learning model was developed using data from 2,571 neonates, including 527 cases (20%) and 2,044 controls (80%). With a mean of 21 features selected, the random forest machine learning approach predicted the outcome with approximately 86.5% balanced accuracy. Factors that were selected a priori through literature-driven variable selection that were also identified as most important by the machine learning model were maternal age, recreational substance exposure, tobacco exposure, intrapartum maternal fever, and low Apgar score at 5 minutes. Additional variables identified through machine learning included in utero alcohol exposure, infertility, miscarriage, primigravida, meconium, spontaneous vaginal delivery, neonatal head circumference, and 1-minute Apgar score. Overall, the machine learning model performed better (area under the curve [AUC] 0.93) than the literature-driven model (AUC 0.73). DISCUSSION: Machine learning may be an alternative, unbiased method to identify clinical predictors associated with PAIS. Identification of previously suggested and novel clinical factors requires cautious interpretation but supports the multifactorial nature of PAIS pathophysiology. Our results suggest that identification of neonates at risk of PAIS is possible.

Risk factors for ischemic stroke in patients with Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms.

BACKGROUND: Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-negative MPNs) are linked with various complications, notably ischemic stroke. The study aims to identify risk factors for ischemic stroke in Ph-negative MPNs patients. METHODS: Patients were categorized into two groups based on whether they had experienced ischemic stroke. Subsequently, an analysis of demographics, biochemical makers, and genetic mutations (JAK2V617F and CALR mutations), was conducted to identify potential associations with an elevated risk of ischemic stroke in individuals with Ph-negative MPNs. RESULTS: A total of 185 patients diagnosed with Ph-negative MPNs participated in the study, including 82 with essential thrombocythemia (ET), 78 with polycythemia vera (PV), and 25 with primary myelofibrosis (PMF). Among these, 57 patients (30.8 %) had a history of ischemic stroke. Independent risk factors associated with ischemic stroke in Ph-negative MPNs patients included hypertension (OR = 5.076) and smoking (OR = 5.426). Among ET patients, smoking (OR = 4.114) and an elevated percentage of neutrophils (OR = 1.080) were both positively correlated with ischemic stroke incidence. For PV patients, hypertension (OR = 4.647), smoking (OR = 6.065), and an increased percentage of lymphocytes (OR = 1.039) were independently associated with ischemic stroke. Regardless of the presence of the JAK2V617F mutation, hypertension was the sole positively and independently associated risk factor for ischemic stroke. The odds ratios for patients with the JAK2V617F mutation was 3.103, while for those without the mutation, it was 11.25. CONCLUSIONS: Hypertension was a more substantial factor associated with an increased incidence of ischemic stroke in Ph-negative MPNs patients.

Racial Disparities in Blood Pressure at Time of Acute Ischemic Stroke Presentation: A Population Study.

BACKGROUND: Hypertension is a stroke risk factor with known disparities in prevalence and management between Black and White patients. We sought to identify if racial differences in presenting blood pressure (BP) during acute ischemic stroke exist. METHODS AND RESULTS: Adults with acute ischemic stroke presenting to an emergency department within 24 hours of last known normal during study epochs 2005, 2010, and 2015 within the Greater Cincinnati/Northern Kentucky Stroke Study were included. Demographics, histories, arrival BP, National Institutes of Health Stroke Scale score, and time from last known normal were collected. Multivariable linear regression was used to determine differences in mean BP between Black and White patients, adjusting for age, sex, National Institutes of Health Stroke Scale score, history of hypertension, hyperlipidemia, smoking, stroke, body mass index, and study epoch. Of 4048 patients, 853 Black and 3195 White patients were included. In adjusted analysis, Black patients had higher presenting systolic BP (161 mm Hg [95% CI, 159-164] versus 158 mm Hg [95% CI, 157-159], P<0.01), diastolic BP (86 mm Hg [95% CI, 85-88] versus 83 mm Hg [95% CI, 82-84], P<0.01), and mean arterial pressure (111 mm Hg [95% CI, 110-113] versus 108 mm Hg [95% CI, 107-109], P<0.01) compared with White patients. In adjusted subanalysis of patients <4.5 hours from last known normal, diastolic BP (88 mm Hg [95% CI, 86-90] versus 83 mm Hg [95% CI, 82-84], P<0.01) and mean arterial pressure (112 mm Hg [95% CI, 110-114] versus 108 mm Hg [95% CI, 107-109], P<0.01) were also higher in Black patients. CONCLUSIONS: This population-based study suggests differences in presenting BP between Black and White patients during acute ischemic stroke. Further study is needed to determine whether these differences influence clinical decision-making, outcome, or clinical trial eligibility.

Sex differences in clinical risk factors in obese ischemic stroke patients with a history of smoking.

Clinical risk factors associated obesity and smoking, as well as their combined effect, are not fully understood. This study aims to determine sex differences in risk factors in a population of acute ischemic stroke (AIS) patients who are obese and with a history of previous or current smoking. METHODS: A retrospective analysis of risk factors in male and female AIS patients with baseline data of obesity and current or previous history of smoking, smoking, and obesity alone was determined. The primary predictor and outcome are risk factors associated with male and female AIS patients. Baseline risk factors were analyzed using a multivariate regression analysis to determine specific risk factors linked with the combined effect of obesity and current or previous history of smoking''. RESULTS: Male obese AIS patients who are current or previous smokers were more likely to be older patients(OR = 1.024, 95% CI, 1.022-1.047, P = 0.033) that present with coronary artery disease (OR = 1.806, 95% CI, 1.028-3.174, P = 0.040), a history of alcohol use (OR = 2.873, 95% CI, 1.349-6.166, P = 0.006), elevated serum creatinine (OR = 4.724, 95% CI, 2.171-10.281, P < 0.001) and systolic blood pressure (OR = 1.029, 95% CI, 1.011-1.047, P < 0.002). Females were more associated with depression (OR = 0.432, 95% CI, 0.244-0.764, P = 0.004), previous TIA (OR = 0.319, 95% CI, 0.142-0.714, P < 0.005), and higher levels of HDL (OR = 0.938, 95% CI, 0.915-0.962, P < 0.001). CONCLUSION: Our results reveal sex differences in risk factors in obese AIS patients with a current or past history of smoking. This finding emphasizes the need to develop management strategies to improve the care of obese AIS patients who are either current or former smokers.

Prediction of aneurysmal subarachnoid hemorrhage in comparison with other stroke types using routine care data.

Aneurysmal subarachnoid hemorrhage (aSAH) can be prevented by early detection and treatment of intracranial aneurysms in high-risk individuals. We investigated whether individuals at high risk of aSAH in the general population can be identified by developing an aSAH prediction model with electronic health records (EHR) data. To assess the aSAH model's relative performance, we additionally developed prediction models for acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) and compared the discriminative performance of the models. We included individuals aged ≥35 years without history of stroke from a Dutch routine care database (years 2007-2020) and defined outcomes aSAH, AIS and ICH using International Classification of Diseases (ICD) codes. Potential predictors included sociodemographic data, diagnoses, medications, and blood measurements. We cross-validated a Cox proportional hazards model with an elastic net penalty on derivation cohorts and reported the c-statistic and 10-year calibration on validation cohorts. We examined 1,040,855 individuals (mean age 54.6 years, 50.9% women) for a total of 10,173,170 person-years (median 11 years). 17,465 stroke events occurred during follow-up: 723 aSAH, 14,659 AIS, and 2,083 ICH. The aSAH model's c-statistic was 0.61 (95%CI 0.57-0.65), which was lower than the c-statistic of the AIS (0.77, 95%CI 0.77-0.78) and ICH models (0.77, 95%CI 0.75-0.78). All models were well-calibrated. The aSAH model identified 19 predictors, of which the 10 strongest included age, female sex, population density, socioeconomic status, oral contraceptive use, gastroenterological complaints, obstructive airway medication, epilepsy, childbirth complications, and smoking. Discriminative performance of the aSAH prediction model was moderate, while it was good for the AIS and ICH models. We conclude that it is currently not feasible to accurately identify individuals at increased risk for aSAH using EHR data.

Association Between Changes in Smoking Habits and Incident Fracture After Acute Ischemic Stroke.

BACKGROUND: Survivors of stroke, particularly the older population, are at an increased risk of falls and incident fractures. Smoking is a widely recognized risk factor for fractures. However, the association between changes in smoking habits before and after an index stroke and increased risk of fracture remains unelucidated. METHODS AND RESULTS: Using the Korean National Health Insurance program, patients with ischemic stroke between 2010 and 2016 were enrolled. Individuals were classified by smoking habits: "never smoker," "former smoker," "smoking quitter," "new smoker," and "sustained smoker." The primary outcome was the composite outcome of the vertebral, hip, and any fractures. Multivariable Cox proportional hazards regression analysis was conducted, using the never-smoker group as the reference. Among 177 787 patients with health screening data within 2 years before and after ischemic stroke, 14 991 (8.43%) patients had any fractures. After multivariable adjustment, the sustained smokers had a significantly increased risk of composite primary outcomes of any, vertebral, and hip fractures (adjusted HR [aHR], 1.222 [95% CI, 1.124-1.329]; aHR, 1.27 [95% CI, 1.13-1.428]; aHR, 1.502 [95% CI, 1.218-1.853], respectively). Additionally, the new smoker group exhibited a similar or higher risk of any fractures and hip fractures (aHR, 1.218 [95% CI, 1.062-1.397]; aHR, 1.772 [95% CI, 1.291-2.431], respectively). CONCLUSIONS: Sustained smokers had a significantly increased risk of vertebral and hip fractures after an ischemic stroke. The risk of any hip fractures was higher in new smokers after ischemic stroke. As poststroke fractures are detrimental to the rehabilitation process of patients with stroke, physicians should actively advise patients to stop smoking.