Effectiveness, utilisation and cost associated with implantable loop recorders versus external monitors after ischaemic or cryptogenic stroke.

OBJECTIVE: Implantable loop recorders (ILRs) are increasingly used for long-term rhythm monitoring after ischaemic and cryptogenic stroke, with the goal of detecting atrial fibrillation (AF) and subsequent initiation of oral anticoagulation to reduce risk of adverse clinical outcomes. There is a need to determine the effectiveness of different rhythm monitoring strategies in this context. METHODS: We conducted a retrospective cohort analysis of individuals with commercial and Medicare Advantage insurance in Optum Labs Data Warehouse who had incident ischaemic or cryptogenic stroke and no prior cardiovascular implantable electronic device from 1 January 2016 to 30 June 2021. Patients were stratified by rhythm monitoring strategy: ILR, long-term continuous external cardiac monitor (>48 hours to 30 days) or Holter monitor (≤48 hours). The primary outcome was risk-adjusted all-cause mortality at 12 months. Secondary outcomes included new diagnosis of AF and oral anticoagulation, bleeding, and costs. RESULTS: Among 48 901 patients with ischaemic or cryptogenic stroke, 9235 received an ILR, 29 103 long-term continuous external monitor and 10 563 Holter monitor only. Mean age was 69.9 (SD 11.9) years and 53.5% were female. During the 12-month follow-up period, patients who received ILRs compared with those who received long-term continuous external monitors had a higher odds of new diagnosis of AF and oral anticoagulant initiation (adjusted OR 2.27, 95% CI 2.09 to 2.48). Compared with patients who received long-term continuous external monitors, those who received ILRs had similar 12-month mortality (HR 1.00; 95% CI 0.89 to 1.12), with approximately $13 000 higher costs at baseline (including monitor cost) and $2500 higher costs during 12-month follow-up. CONCLUSIONS: In this large real-world study of patients with ischaemic or cryptogenic stroke, ILR placement resulted in more diagnosis of AF and initiation of oral anticoagulation, but no difference in mortality compared with long-term continuous external monitors.

Revealing the pharmacological mechanisms of nao-an dropping pill in preventing and treating ischemic stroke via the PI3K/Akt/eNOS and Nrf2/HO-1 pathways.

Nao-an Dropping Pill (NADP) is a Chinese patent medicine which commonly used in clinic for ischemic stroke (IS). However, the material basis and mechanism of its prevention or treatment of IS are unclear, then we carried out this study. 52 incoming blood components were resolved by UHPLC-MS/MS from rat serum, including 45 prototype components. The potential active prototype components hydroxysafflor yellow A, ginsenoside F1, quercetin, ferulic acid and caffeic acid screened by network pharmacology showed strongly binding ability with PIK3CA, AKT1, NOS3, NFE2L2 and HMOX1 by molecular docking. In vitro oxygen-glucose deprivation/reperfusion (OGD/R) experimental results showed that NADP protected HA1800 cells from OGD/R-induced apoptosis by affecting the release of LDH, production of NO, and content of SOD and MDA. Meanwhile, NADP could improve behavioral of middle cerebral artery occlusion/reperfusion (MCAO/R) rats, reduce ischemic area of cerebral cortex, decrease brain water and glutamate (Glu) content, and improve oxidative stress response. Immunohistochemical results showed that NADP significantly regulated the expression of PI3K, Akt, p-Akt, eNOS, p-eNOS, Nrf2 and HO-1 in cerebral ischemic tissues. The results suggested that NADP protects brain tissues and ameliorates oxidative stress damage to brain tissues from IS by regulating PI3K/Akt/eNOS and Nrf2/HO-1 signaling pathways.

In mild ischemic stroke or high-risk TIA, DAPT started ≤72 h after onset reduced new stroke and increased bleeding at 90 d.

SOURCE CITATION: Gao Y, Chen W, Pan Y, et al; INSPIRES Investigators. Dual antiplatelet treatment up to 72 hours after ischemic stroke. N Engl J Med. 2023;389:2413-2424. 38157499.

Trends in Dual Antiplatelet Therapy of Aspirin and Clopidogrel and Outcomes in Ischemic Stroke Patients Noneligible for POINT/CHANCE Trial Treatment.

BACKGROUND: Recent clinical trials established the benefit of dual antiplatelet therapy with aspirin and clopidogrel (DAPT-AC) in early-presenting patients with minor ischemic stroke. However, the impact of these trials over time on the use and outcomes of DAPT-AC among the patients with nonminor or late-presenting stroke who do not meet the eligibility criteria of these trials has not been delineated. METHODS AND RESULTS: In a multicenter stroke registry, this study examined yearly changes from April 2008 to August 2022 in DAPT-AC use for stroke patients ineligible for CHANCE/POINT (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events/Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) clinical trials due to National Institutes of Health Stroke Scale >4 or late arrival beyond 24 hours of onset. A total of 32 118 patients (age, 68.1±13.1 years; male, 58.5%) with National Institutes of Health Stroke Scale of 4 (interquartile range, 1-7) were analyzed. In 2008, DAPT-AC was used in 33.0%, other antiplatelets in 62.7%, and no antiplatelet in 4.3%. The frequency of DAPT-AC was relatively unchanged through 2013, when the CHANCE trial was published, and then increased steadily, reaching 78% in 2022, while other antiplatelets decreased to 17.8% in 2022 (Ptrend<0.001). From 2011 to 2022, clinical outcomes nonsignificantly improved, with an average relative risk reduction of 2%/y for the composite of stroke, myocardial infarction, and all-cause mortality, both among patients treated with DAPT-AC and patients treated with other antiplatelets. CONCLUSIONS: Use of DAPT-AC in stroke patients with stroke ineligible for recent DAPT clinical trials increased markedly and steadily after CHANCE publication in 2013, reaching deployment in nearly 4 of every 5 patients by 2022. The secondary prevention in patients with ischemic stroke seems to be gradually improving, possibly due to the enhancement of risk factor control.

ZOom Delivered Intervention Against Cognitive decline (ZODIAC) COVID-19 pandemic adaptations to the Post-Ischaemic Stroke Cardiovascular Exercise Study (PISCES): protocol for a randomised controlled trial of remotely delivered fitness training for brain health.

BACKGROUND: Stroke increases subsequent dementia risk yet there are no specific post-stroke therapies to protect cognition. Cardiorespiratory exercise is recommended for secondary prevention of stroke and may be neuroprotective. The Post Ischaemic Stroke Cardiovascular Exercise Study (PISCES) aims to reduce post-stroke secondary neurodegeneration and cognitive decline. During the pandemic, we pivoted to a ZOom Delivered Intervention Against Cognitive decline (ZODIAC) protocol, reducing pandemic-amplified barriers to exercise. METHODS: We present pandemic adaptions for a multicentre phase IIb assessor-blinded randomised controlled trial of ischaemic stroke survivors testing the efficacy and feasibility of an 8-week home-based exercise intervention delivered at 2 months post-stroke. We compare cardiorespiratory exercise (intervention arm) versus balance and stretching (active control arm). Participants are assessed with magnetic resonance imaging (MRI), fitness, blood, microbiome, and neuropsychological tests at three study visits: before and after the exercise intervention and at 12 months. Modifications to the original protocol include pre-exercise safety home visits, commercial delivery of exercise equipment to facilitate assessor blinding, and reconsideration of statistical plan to allow pooling of the studies. We have reduced in-person study visits from 27 to 3. Primary outcome remains between-group (intervention versus control) difference in brain volume change; secondary outcome is between-group difference in global cognitive ability to allow remote administration of a validated cognitive scale. DISCUSSION: Remotely delivered exercise interventions reduce participant burden and may reduce barriers to recruitment. A decrease in the number of in-person study visits can be supported by greater information capture via self-reported questionnaires and phone surveys. TRIAL REGISTRATION: Prospectively ACTRN12616000942459. Registered on July 2016.

Effects of a Planned Web-Based Educational Intervention Based on the Health Belief Model for Patients With Ischemic Stroke in Promoting Secondary Prevention During the COVID-19 Lockdown in China: Quasi-Experimental Study.

Background: Some common modified vascular risk factors remain poorly controlled among stroke survivors, and educational programs may help improve these conditions. Objective: This study aimed to evaluate the effect of a planned web-based educational intervention based on the health belief model (HBM) in promoting secondary prevention among patients with ischemic stroke. Methods: An evaluation-blinded quasi-experimental trial with a historical control group was conducted. Patients admitted from March to June 2020 were assigned to the historical control group, and patients admitted from July to October 2020 were assigned to the intervention group. The control group received routine health management. The intervention group received 6 additional sessions based on the HBM via Tencent Meeting, an audio and video conferencing application, within 3 months after discharge. Sessions were held every 2 weeks, with each session lasting approximately 40 minutes. These sessions were conducted in small groups, with about 8 to 10 people in each group. The primary outcomes were changes in blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), hemoglobin A1c (HbA1c), and the proportion of patients achieving the treatment target. The secondary outcomes were medication adherence, assessed with the Morisky Medicine Adherence Scale (MMAS), and disability, assessed with the modified Rankin scale. Results: In total, 315 patients experiencing their first-ever stroke were analyzed. More patients in the intervention group had controlled BP (41.9% vs 28.4%; adjusted odds ratio [aOR] 1.93; P=.01), LDL-C (83.1% vs 67.7%; aOR 2.66; P=.001), and HbA1c (91.9% vs 83.9%; aOR: 3.37; P=.04) levels as well as a significant postintervention decrease in the systolic BP (adjusted ß -3.94; P=.02), LDL-C (adjusted ß -0.21; P=.008), and HbA1c (adjusted ß -0.27; P<.001), compared with control groups. Significant between-group differences were observed in medication adherence (79.4% vs 63.2%; aOR 2.31; P=.002) but not in favorable functional outcomes. Conclusions: A web-based education program based on the HBM may be more effective than current methods used to educate patients having strokes on optimal vascular risk factors and medication adherence.

Outcomes of non-vitamin K oral anticoagulants for secondary prevention in ischemic stroke with atrial fibrillation.

Previous studies have rarely investigated the role of non-vitamin K oral anticoagulants (NOAC) and warfarin in the secondary prevention of ischemic stroke patients with nonvalvular atrial fibrillation (NVAF). In this study, we compared the effectiveness and safety of NOAC and warfarin for secondary prevention in Korean ischemic stroke patients with NVAF. Based on the Korean National Health Insurance Service Database, this study included 21,064 oral anticoagulants-naïve acute ischemic stroke patients with NVAF between July 2015 and June 2019. The main study outcomes included ischemic stroke, systemic embolism, major bleeding, and death. During the observational periods, NOAC users had a significantly decreased risk of ischemic stroke + systemic embolism (adjusted hazard ratio [aHR] 0.86; 95% confidence interval [CI] 0.78-0.95), ischemic stroke (aHR 0.89; 95% CI 0.81-0.99), major bleeding (aHR 0.78; 95% CI 0.68-0.89), and all-cause death (aHR 0.87; 95% CI 0.81-0.93). Standard-dose NOAC users had a lower risk of ischemic stroke, systemic embolism, and major bleeding events than warfarin users. In contrast, low-dose NOAC users did not differ in risk from warfarin users for all outcomes. In conclusion, NOACs were associated with a lower risk of secondary thromboembolic events and bleeding complications in Korean ischemic stroke patients with NVAF than warfarin.

Ischaemic stroke in women with atrial fibrillation: temporal trends and clinical implications.

BACKGROUND AND AIMS: Female sex has been linked with higher risk of ischaemic stroke (IS) in atrial fibrillation (AF), but no prior study has examined temporal trends in the IS risk associated with female sex. METHODS: The registry-linkage Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study included all patients with AF in Finland from 2007 to 2018. Ischaemic stroke rates and rate ratios were computed. RESULTS: Overall, 229 565 patients with new-onset AF were identified (50.0% women; mean age 72.7 years). The crude IS incidence was higher in women than in men across the entire study period (21.1 vs. 14.9 events per 1000 patient-years, P < .001), and the incidence decreased both in men and women. In 2007-08, female sex was independently associated with a 20%-30% higher IS rate in the adjusted analyses, but this association attenuated and became statistically non-significant by the end of the observation period. Similar trends were observed when time with and without oral anticoagulant (OAC) treatment was analysed, as well as when only time without OAC use was considered. The decrease in IS rate was driven by patients with high IS risk, whereas in patients with low or moderate IS risk, female sex was not associated with a higher IS rate. CONCLUSIONS: The association between female sex and IS rate has decreased and become non-significant over the course of the study period from 2007 to 2018, suggesting that female sex could be omitted as a factor when estimating expected IS rates and the need for OAC therapy in patients with AF.

Trends in the Use of Medications for Secondary Ischemic Stroke Prevention in Denmark, 2005-2021.

BACKGROUND AND OBJECTIVES: Understanding trends in the use of medications for secondary stroke prevention is crucial for identifying areas for improvement in stroke care. We examined the use of lipid-lowering, antihypertensive, glucose-lowering, oral anticoagulant, and antiplatelet medications after ischemic stroke hospitalization, from 2005 to 2021. METHODS: Using nationwide registries in Denmark, we identified a cohort of patients discharged from hospital with a first-time or recurrent ischemic stroke (N = 150,744). Stratified by calendar year, we ascertained the 180-day probability of filling a prescription for the abovementioned medications after discharge. We further assessed factors associated with medication use. RESULTS: From 2005 to 2021, lipid-lowering medication use increased from 58.3% to 82.0%; atorvastatin use rose from 2.1% to 64.8% and simvastatin use decreased from 55.7% to 8.6%. Antihypertensive medication use remained stable, at approximately 89%, and various antihypertensive classes were used comparably. Glucose-lowering medication use increased from 71.5% in 2005 to 84.1% in 2021, driven primarily by an increase in metformin use (from 28.0% to 59.5%). Use of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors continually increased (from 1.7% to 17.5% and from 0.5% to 17.3%, respectively) between 2015 and 2021. Anticoagulant medication use rose from 45.9% in 2005 to 87.0% in 2021, primarily because of increased use of direct oral anticoagulant medications starting around 2010 and a decline in warfarin use. Antiplatelet use remained consistently high, at approximately 95%. Trends were consistent across subgroups of interest; however, overall medication use was lower in older patients (65 years and older), patients with severe stroke, and patients with neurologic and psychiatric comorbidities. DISCUSSION: Despite increasing trends in the use of 3 of 5 medication classes, the overall use of lipid-lowering, glucose-lowering, and oral anticoagulant medications was somewhat lower than expected according to clinical guidelines, particularly among older patients with more severe stroke and other comorbidities. The relatively low use in these subgroups may signify appropriate clinical decision making in consideration of frequent contraindications and reduced life expectancy or highlight potential areas of improvement for the care of patients with recent ischemic stroke.

The discovery of GGT1 as a novel gene for ischemic stroke conferring protection against disease risk in non-smokers and non-abusers of alcohol.

OBJECTIVES: Increased plasma gamma-glutamyl transferase (GGT1) has been identified as a robust and independent risk factor for ischemic stroke (IS), but the molecular mechanisms of the enzyme-disease association are unclear. The present study investigated whether polymorphisms in the GGT1 gene contribute to IS susceptibility. MATERIALS AND METHODS: DNA samples obtained from 1288 unrelated individuals (600 IS patients and 688 controls) were genotyped for common single nucleotide polymorphisms of GGT1 using the MassArray-4 platform. RESULTS: The rs5751909 polymorphism was significantly associated with decreased risk of ischemic stroke regardless sex and age (Pperm ≤ 0.01, dominant genetic model). The haplotype rs4820599A-rs5760489A-rs5751909A showed strong protection against ischemic stroke (OR 0.53, 95 %CI 0.36 - 0.77, Pperm ≤ 0.0001). The protective effect of SNP rs5751909 in the stroke phenotype was successfully replicated in the UK Biobank, SiGN, and ISGC cohorts (P ≤ 0.01). GGT1 polymorphisms showed joint (epistatic) effects on the risk of ischemic stroke, with some known IS-associated GWAS loci (e.g., rs4322086 and rs12646447) investigated in our population. In addition, SNP rs5751909 was found to be strongly associated with a decreased risk of ischemic stroke in non-smokers (OR 0.54 95 %CI 0.39-0.75, Pperm = 0.0002) and non-alcohol abusers (OR 0.43 95 %CI 0.30-0.61, Pperm = 2.0 × 10-6), whereas no protective effects of this SNP against disease risk were observed in smokers and alcohol abusers (Pperm < 0.05). CONCLUSIONS: We propose mechanisms underlying the observed associations between GGT1 polymorphisms and ischemic stroke risk. This pilot study is the first to demonstrate that GGT1 is a novel susceptibility gene for ischemic stroke and provides additional evidence of the genetic contribution to impaired redox homeostasis underlying disease pathogenesis.

Preconditioning exercise reduces brain damage of ischemic stroke in rats via PI3K-AKT pathway by bioinformatic analysis.

Ischemic stroke is one of the most vital causes of high neurological morbidity and mortality in the world. Preconditioning exercise is considered as the primary prevention of stroke to resistance to subsequent injury. We tried to research the underlying biological mechanisms of this exercise. Forty-two SD rats were randomly divided into three groups: middle cerebral artery occlusion (MCAO) group, exercise group with MCAO (EX + MCAO) group, and sham group, with 14 rats in each group. The EX + MCAO group underwent exercise preconditioning for 3 weeks before occlusion, and the other two groups were fed and exercised normally. After 3 weeks, MCAO model was made by thread plug method in the EX + MCAO group and MCAO group. After successful modeling, the Longa scale was used to evaluate the neurological impairment of rats at day 0, day 1, and day 2. The rats in each group were killed on the third day after modeling. TTC staining measured the infarct volume of each group. The morphology and apoptosis of cortical cells were observed by HE and Tunel staining. Three rats in each group underwent high-throughput sequencing. Bioinformatic analysis was used to find the deferentially expressed genes (DEGs) and predict the transcription factor binding sites (TFBS) of the next-generation sequencing results. Gene enrichment (GSEA) was used to analyze potential functional genes and their corresponding signaling pathways. The Longa scale showed EX + MCAO group had the neurological function better than the modeling group (P < 0.001). TTC staining showed that the infarct size of EX + MCAO group was less than MCAO group (P < 0.05). HE and Tunel staining showed that the cells in the EX + MCAO group and the sham group had normal morphology and fewer apoptotic cells than MCAO group. A new gene named 7994 was discovered and TFBS of this gene was predicted, which could interact with key genes such as Foxd3, Foxa2, NR4A2, SP1, CEBPA, and SOX10. GSEA showed that EX + MCAO group could promote and regulate angiogenesis and apoptosis through PI3K-AKT pathway. Preconditioning exercise could improve nerve function and reduce infarct size in rats. The underlying mechanism is to regulate the PI3K-AKT pathway through several key genes, promote cerebral angiogenesis, and reduce apoptosis.

Comparative Safety and Effectiveness of Reduced Doses of Direct Acting Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation.

BACKGROUND: This Nordic observational cohort study aims to assess the effectiveness and safety of reduced-dose direct-acting oral anticoagulants (DOACs) dabigatran, rivaroxaban, and apixaban compared to standard warfarin for stroke prevention in nonvalvular atrial fibrillation. METHODS: The study, utilizing nationwide administrative databases from Denmark, Sweden, Norway, and Finland, spanned from January 1, 2011 to December 31, 2018 (2017 for Sweden). The cohort included 26,883 patients initiating reduced-dose DOACs and 108,014 comparable warfarin patients. Effectiveness was measured by the composite endpoint of ischemic stroke and systemic embolism, while safety was assessed through intracranial hemorrhage. RESULTS: The meta-analysis across countries revealed similar or lower incidences of ischemic stroke and systemic embolism in patients on reduced-dose DOACs compared to standard warfarin (rivaroxaban: HR 0.93, dabigatran: HR 0.88, apixaban: HR 0.79). Incidences within warfarin groups ranged from 2.16 to 3.71 per 100 person-years, comparable to DOAC recipients. Intracranial hemorrhage rates were generally low, ranging from 0.16 to 1.85 per 100 person-years. In comparison with warfarin patients, meta-analyses yielded HRs for rivaroxaban (1.41), dabigatran (0.35), and apixaban (0.72). CONCLUSIONS: In this study, atrial fibrillation patients initiating reduced-dose rivaroxaban and dabigatran exhibited incidences of ischemic stroke and systemic embolism similar to warfarin, and for apixaban, even lower. Rates of intracranial hemorrhage were comparable to or lower for patients on DOACs compared to warfarin.

Outcomes Associated With Left Atrial Appendage Occlusion Via Implanted Device in Atrial Fibrillation.

OBJECTIVE: To compare outcomes after left atrial appendage occlusion (LAAO) via implanted device vs no LAAO in a matched cohort of patients with atrial fibrillation (AF). METHODS: This longitudinal retrospective cohort study was based on the national database covering hospital care for the entire French population. Adults (≥18 years of age) who had been hospitalized with AF (January 1, 2015, to January 1, 2020) who underwent LAAO were identified. Propensity score matching was used to control for potential confounders of the treatment-outcome relationship. The primary outcome was a composite of ischemic stroke, major bleeding, or all-cause death during follow-up. RESULTS: After propensity score matching, 1216 patients with AF who were treated with LAAO were matched with 1216 controls (patients AF who were not treated with LAAO). Mean follow-up was 14.5 months (median, 13 months; IQR, 7-21 months). Patients with LAAO had a lower risk of the composite outcome (HR, 0.48; 95% CI, 0.42 to 0.55). Total events (309 for LAAO vs 640 for controls) and event rates (23.3% vs 44.0%/year, respectively) were lower for LAAO, driven primarily by a decreased risk of all-cause death (HR, 0.39; 95% CI, 0.33 to 0.46; P<.0001), whereas ischemic stroke risk was higher (HR, 1.75; 95% CI, 1.17 to 2.64). Significant interactions were observed in subgroups with a history of ischemic stroke (P<.001) and of bleeding (P=.002). CONCLUSION: Among AF patients at high bleeding risk, our nationwide study highlights a high risk of clinical events during follow-up. LAAO appeared less effective than no LAAO in preventing stroke but more effective in preventing death. Left atrial appendage occlusion is particularly effective in patients with previous ischemic stroke or any episode of bleeding.

Changing or Retaining Direct Oral Anticoagulant After Ischemic Stroke Despite Direct Oral Anticoagulant Treatment.

BACKGROUND: The optimal antithrombotic strategies for patients with atrial fibrillation who experience ischemic stroke (IS) despite direct oral anticoagulant (DOAC) therapy remain inconclusive. This study compared outcomes for patients with DOAC treatment failure who changed or retained their prestroke DOAC. METHODS AND RESULTS: This retrospective cohort study analyzed data from the National Health Insurance Research Database from 2012 to 2020. Patients with atrial fibrillation who experienced IS during DOAC therapy were assigned to either (1) the DOAC-change group: changing prestroke DOAC or (2) the DOAC-retain group: retaining prestroke DOAC. The primary outcome was a composite of recurrent IS and transient ischemic attack. The secondary outcomes included intracranial hemorrhage, major bleeding, systemic thromboembolism, and all-cause death. Propensity score-based inverse probability of treatment weighting was applied to balance the baseline characteristics between the DOAC-change and DOAC-retain groups. The Cox proportional hazards model compared the risk of outcomes between the 2 groups. In total, 1979 patients were enrolled (609 DOAC-change patients and 1370 DOAC-retain patients). The incidence rates of recurrent IS or transient ischemic attack were 7.20 and 6.56 per 100 person-years in the DOAC-change and DOAC-retain groups, respectively (hazard ratio [HR], 1.07 [95% CI, 0.87-1.30]). A nonsignificantly higher incidence rate of intracranial hemorrhage was observed in the DOAC-change group compared with the DOAC-retain group (0.75 versus 0.53 per 100-person-years; HR, 1.49 [95% CI, 0.78-2.83]). The systemic thromboembolism, major bleeding, and death rates were comparable between the DOAC-change and DOAC-retain groups. CONCLUSIONS: Changing prestroke DOAC does not reduce the risk of recurrent cerebral ischemia in patients with atrial fibrillation who develop IS during DOAC therapy. However, future studies should continue to observe the potential trends of increased intracranial hemorrhage risk.

Spicy food consumption reduces the risk of ischaemic stroke: a prospective study.

Previous studies revealed that consuming spicy food reduced mortality from CVD and lowered stroke risk. However, no studies reported the relationship between spicy food consumption, stroke types and dose­response. This study aimed to further explore the association between the frequency of spicy food intake and the risk of stroke in a large prospective cohort study. In this study, 50 174 participants aged 30­79 years were recruited. Spicy food consumption data were collected via a baseline survey questionnaire. Outcomes were incidence of any stroke, ischaemic stroke (IS) and haemorrhagic stroke (HS). Multivariable-adjusted Cox proportional hazard models estimated the association between the consumption of spicy food and incident stroke. Restricted cubic spline analysis was used to examine the dose­response relationship. During the median 10·7-year follow-up, 3967 strokes were recorded, including 3494 IS and 516 HS. Compared with those who never/rarely consumed spicy food, those who consumed spicy food monthly, 1­2 d/week and 3­5 d/week had hazard ratio (HR) of 0·914 (95 % CI 0·841, 0·995), 0·869 (95 % CI 0·758, 0·995) and 0·826 (95 % CI 0·714, 0·956) for overall stroke, respectively. For IS, the corresponding HR) were 0·909 (95 % CI 0·832, 0·994), 0·831 (95 % CI 0·718, 0·962) and 0·813 (95 % CI 0·696, 0·951), respectively. This protective effect showed a U-shaped dose­response relationship. For obese participants, consuming spicy food ≥ 3 d/week was negatively associated with the risk of IS. We found the consumption of spicy food was negatively associated with the risk of IS and had a U-shaped dose­response relationship with risk of IS. Individuals who consumed spicy food 3­5 d/week had a significantly lowest risk of IS.

Risk of stroke in patients with prior VKA or DOAC: A population-based real-world registry analysis.

INTRODUCTION: To date, risk assessment of suffering ischemic and hemorrhagic stroke in individuals under oral anticoagulation (OAC) is limited to hospital-based cohorts and patients with atrial fibrillation. PATIENTS AND METHODS: Through the combination of three individual datasets, (1) the population-based Tyrolean Stroke Pathway database, prospectively documenting all (unselected) stroke patients in the entire federal state of the Tyrol and (2) nation-wide prescription data, detailing each reimbursed prescription in Austria as well as (3) the Austrian Stroke Unit Registry, a nation-wide registry comprising data on all patients admitted to any of the 38 stroke units in Austria, we assessed risk of stroke in patients with prior oral anticoagulation and compared characteristics of patients taking direct oral anticoagulants and Vitamin-K-Antagonists. RESULTS: In Austria, oral anticoagulant prescription reimbursements increased from 292,475 in 2015 to 389,407 in 2021. In the Tyrol, prior oral anticoagulation treatment was evident in 586 of 3861 (15.2%) patients with ischemic and 131 of 523 (25.0%) with hemorrhagic stroke, with 20% and 35% of those stroke patients respectively having prior oral anticoagulation due to other indications than non-valvular atrial fibrillation. Considering prescription rates, treatment with direct oral anticoagulants was associated with a reduced stroke risk compared to Vitamin-K-Antagonists, especially in ischemic (1.05% vs 0.62%; RR 0.59, p < 0.001) but also in hemorrhagic stroke, even if less pronounced (0.21% vs 0.14%; RR 0.68, p = 0.06). In Austria, prior intake of direct oral anticoagulants was associated with lower risk of suffering acute large vessel occlusion stroke (RR 0.79, p = 0.003). DISCUSSION AND CONCLUSIONS: One in seven patients suffering ischemic and one in four suffering hemorrhagic stroke had prior oral anticoagulation treatment. Both ischemic and hemorrhagic strokes are less frequent in those with direct oral anticoagulant intake compared to those taking Vitamin-K-Antagonists. Establishment of clear standard operating procedures on how to best care for acute stroke patients with oral anticoagulation is essential.

Cornuside protects against ischemic stroke in rats by suppressing the IL-17F/TRAF6/NF-κB pathway via the brain-gut axis.

Ischemic stroke is a serious neurological disease with limited therapeutic options; thus, it is particularly important to find effective treatments. Restoration of gut microflora diversity is an important factor in the treatment of ischemic stroke, but the mechanism remains unclear. Cornuside is known for its unique anti-inflammatory and circulation-promoting effects; however, whether it can effectively treat ischemic stroke and its therapeutic mechanisms remain unknown. In this study, we used a rat middle cerebral artery occlusion-reperfusion model (MCAO/R) to mimic ischemic stroke in humans and to assess the cerebral protective effects of cornuside in rats with ischemic stroke. Using 16S rRNA sequencing and RNA sequencing, we explored the cornuside mechanism in the brain-gut axis that confers protection against ischemic stroke. In conclusion, cornuside can inhibit the IL-17F/TRAF6/NF-κB pathway by improving the dysregulation of intestinal microflora, and reduce intestinal inflammation and neuroinflammation, which treated ischemic stroke rats.