Independent Risk Factor For Stroke Research Articles

#850 The association between proteinuria and stroke: results from the non-communicable diseases screening programme of Chiang Mai Region, Northern Thailand

Abstract Background and Aims Stroke is a significant global health issue, representing the second leading cause of death and a major contributor to disability. It can be classified into two main types: ischemic stroke, caused by blockage of a brain blood vessel, and haemorrhagic stroke, resulting from blood vessel rupture. Chronic kidney disease (CKD) is another prevalent health concern, affecting approximately 10% of all populations worldwide. CKD impairs kidney function and has been associated with an increased risk of cerebrovascular events, including stroke. Within the Northern Thai population, the prevalence of CKD is higher than the global average, underscoring the importance of investigating the relationship between CKD and stroke in this region. Method All patients for which accurate proteinuria measurement was obtained as part of the NCD screening program in Chiang Mai, Northern Thailand were included in the study. Multilinear cox regression analysis was used to estimate the hazards ratio for the association between proteinuria on stroke. The model was adjusted for other significant confounders of the association including age, sex, CKD, diabetes, hypertension and hypercholesterolaemia Results In a cohort of 3967 patients for which accurate proteinuria measurements were obtained and for whom had complete data for covariates, there was no evidence for an association between proteinuria and stroke. Hazards ratio for stroke in patients with trace proteinuria (adjusted for covariates) was 1.08 (95% CI 0.80-1.45) and positive proteinuria 0.06 (0.78-1.44) compared to a baseline of no proteinuria. Conclusion This study provides important insights into stroke risk factors in the Northern Thai population. The lack of substantial association between proteinuria and stroke suggests that proteinuria may not independently contribute to stroke risk in this cohort. Generalizability, however, is limited due to overrepresentation of diabetes and hypercholesterolaemia in the cohort, which is a strong independent risk factor for stroke. Increasing age is identified as the most critical risk factor for stroke. Understanding these associations can guide targeted interventions and public health strategies for stroke prevention in this population. The study limitations highlight the importance of analysis of a cohort that is more representative of a wider population in terms of chronic disease, such as diabetes and hypercholesterolaemia, and highlights the importance of longer follow up to fully elucidate whether proteinuria has an association with stroke. Furthermore the study raises questions as to whether measurement of proteinuria via urine dipstick analysis may limit conclusions that can be drawn compared to more robust methods such as urine albumin:creatinine or urine protein:creatinine ratios. Finally this study may be underpowered to detect subtle changes of a hazards ratio of less than 1.2, so is at risk of a type 2 statistical error.

Lipoprotein (a) concentration as a risk factor for ischaemic stroke and its subtypes.

To investigate the relationship between serum lipoprotein (a) [Lp(a)] concentration and the risk of ischaemic stroke (IS) and its subtypes. Lp(a) plays a role in atherogenic, pro-thrombotic, and antifibrinolytic processes. Elevated plasma Lp(a) is a strong independent risk factor for the development and progression of atherosclerotic disease. The association between lipoproteins and IS is more complex than that reported for cardiovascular diseases, with inconsistent and contradictory results from epidemiological studies. 231 patients with acute IS (defined as cases) and 163 age- and sex-matched control subjects were included in this prospective case-control study. Demographic and clinical variables (i.e. age, sex, smoking, presence of chronic diseases and concomitant medication) and laboratory data (i.e. concentrations of total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, Lp(a), apolipoprotein A1, apolipoprotein B) were recorded. The mean age and the percentage of men did not significantly differ between groups. Compared to controls, there was a significantly higher percentage of cases reported with concomitant diseases: diabetes mellitus, myocardial infarction, ischaemic heart disease, peripheral arterial disease, and atrial fibrillation. The study showed a significantly higher serum Lp(a) concentration in cases than in control subjects (81.81 nmol/L [c.32.7 mg/dL] vs. 59.75 nmol/L [c.23.9 mg/dL]; p = 0.036) and found an association between Lp(a) levels stratified by quartiles and the risk for ischaemic stroke (Q1 [Lp(a) < 13 nmol/L] vs. Q4 [Lp(a) > 117 nmol/L]: OR 2.23; 95% CI 1.23-4.03; p = 0.008). A subgroup analysis based on the TOAST classification of IS also showed a significant association between Lp(a) value of more than 75 nmol/L (30 mg/dL) and the risk of large-artery atherosclerosis stroke compared to the controls (OR 2.4; 95% CI 1.39-3.93; p = 0.001), as well as a statistically non-significant association with other subtypes of IS. The influence of Lp(a) remained significant even after adjusting for established risk factors for IS (OR 1.99; 95% CI 1.05-3.76; p = 0.04; respectively for the large-artery atherosclerotic subtype: OR 2.54; 95% CI 1.39-4.67; p = 0.003). We found that Lp(a) is an independent risk factor for ischaemic stroke, and for the large-artery atherosclerotic subtype of ischaemic stroke.

Outcome of Pulmonary Embolism with and without Ischemic Stroke.

Background: Ischemic stroke is the second, and pulmonary embolism (PE) is the third most common cardiovascular cause of death after myocardial infarction. Data regarding risk factors for ischemic stroke in patients with acute PE are limited. Methods: Patients were selected by screening the German nationwide in-patient sample for PE (ICD-code I26) and were stratified by ischemic stroke (ICD code I63) and compared. Results: The nationwide in-patient sample comprised 346,586 hospitalized PE patients (53.3% females) in Germany from 2011 to 2014; among these, 6704 (1.9%) patients had additionally an ischemic stroke. PE patients with ischemic stroke had a higher in-hospital mortality rate than those without (28.9% vs. 14.5%, p < 0.001). Ischemic stroke was independently associated with in-hospital death (OR 2.424, 95%CI 2.278-2.579, p < 0.001). Deep venous thrombosis and/or thrombophlebitis (DVT) combined with heart septal defect (OR 24.714 [95%CI 20.693-29.517], p < 0.001) as well as atrial fibrillation/flutter (OR 2.060 [95%CI 1.943-2.183], p < 0.001) were independent risk factors for stroke in PE patients. Systemic thrombolysis was associated with a better survival in PE patients with ischemic thrombolysis who underwent cardio-pulmonary resuscitation (CPR, OR 0.55 [95%CI 0.36-0.84], p = 0.006). Conclusions: Ischemic stroke did negatively affect the survival of PE. Combination of DVT and heart septal defect and atrial fibrillation/flutter were strong and independent risk factors for ischemic stroke in PE patients. In PE patients with ischemic stroke, who had to underwent CPR, systemic thrombolysis was associated with improved survival.

Correlation between plasma lipoprotein-associated phospholipase A2 levels and risk of ischaemic stroke recurrence by gender in the Chinese population

ABSTRACT Objective To investigate the correlation between gender differences in plasma lipoprotein phospholipase A2 (Lp-PLA2) levels and the risk of recurrent stroke in patients with acute ischaemic stroke in China. Methods We conducted a prospective follow-up study that included baselineLp-PLA2 levels and NIH Stroke Scale (NIHSS) scores in patients with ischaemic stroke upon admission. The diagnostic efficacy of the baseline Lp-PLA2 level for stroke recurrence was evaluated. And Kaplan‒Meier method was used to analyse the difference in the risk of recurrent stroke between these two groups among males and females. A paired t test was used to analyse the difference in Lp-PLA2 levels in male and female patients after follow-up. Results Baseline plasma Lp-PLA2 was higher in men and women with recurrent stroke than in those without recurrent stroke. The correlation between baseline Lp-PLA2 and neurological impairment was higher in female than male stroke patients (R = 0.338 and 0.253, respectively). Although weakly correlated with neurological impairment, baseline Lp-PLA2 was more effective in predicting recurrent stroke (AUC = 0.705 in men, 0.788 in women). A Cox model was used to compare the risk of stroke between the high- and low-Lp-PLA2 groups (OR = 3.98 in men, 2.61 in women). According to the follow-up time of 6 months as the node, Lp-PLA2 will give different risk indicators. Conclusion Elevated plasma Lp-PLA2 is an independent risk factor for recurrent ischaemic stroke but is not strongly associated with the degree of cerebral damage. The predictive value of baseline Lp-PLA2 for stroke recurrence risk was higher in females than in males.

Risk factors for ischemic stroke in China: a case-control study

Background Stroke is a primary cause of disability and death in adults worldwide. This study aimed to determine whether uric acid (UA), total bilirubin (TBIL), serum creatinine (Scr), homocysteine (Hcy), platelet large cell ratio (P-LCR), mean platelet volume (MPV), red blood cell volume distribution width (RDW), and common carotid artery intima-media thickness (CCA-IMT) were risk factors for ischemic stroke and whether there were sex differences in their associations. Methods This was a case-control study, and all data were collected from the medical records at Fuzhou First People’s Hospital of Jiangxi Province, China. The case group consisted of 400 patients treated for ischemic stroke at the Neurology Department, Fuzhou First People’s Hospital from January 2017 to June 2023. The control group included 200 patients with non-ischemic stroke in the same period and at the same hospital. In this study, clinical history, physical examination, and biochemical indices such as UA, TBIL, Scr, Hcy, P-LCR, MPV, and RDW were obtained from the patients’ medical records. Craniocerebral imaging was performed using magnetic resonance imaging (MRI) or computerized tomography (CT). CCA-IMT was measured using ultrasonography of the carotid arteries. Results In the multivariate binary logistic regression analysis, Hcy, FBS, right CCA-IMT and Hypertension were associated with ischemic stroke (p&lt;0.001). The odds of ischemic stroke increased with Hcy (adjusted OR=1.217, 95% CI=1.129-1.311, p&lt;0.001), fasting blood sugar (FBS) (adjusted OR=1.313, 95%CI=1.169-1.475, p&lt;0.001), and right CCA-IMT (adjusted OR=45.273, 95%CI=6.693-306.232, p&lt;0.001). Hypertensive persons had a higher possibility of ischemic stroke than persons without hypertension (adjusted OR=3.161, 95%CI=2.086-4.790, p&lt;0.001). Conclusions Hcy, FBS, right CCA-IMT, and hypertension are independent risk factors for ischemic stroke in China. There was no association between TBIL, Scr, P-LCR, MPV, RDW, and the incidence of ischemic stroke. There was no sex difference in the association between Hcy, TBIL, Scr, P-LCR, and the incidence of ischemic stroke.

Diagnostic and prediction value of synthetic magnetic resonance imaging in acute ischemic stroke patients.

Current knowledge regarding synthetic magnetic resonance imaging in ischemic stroke (MAGiC) is inadequate. The study aimed to investigate the diagnostic and prognostic prediction value of MAGiC in acute ischemic stroke (AIS) patients. This prospective observational study enrolled 197 AIS patients between January 2022 and May 2023. All patients underwent routine magnetic resonance imaging (MRI), computed tomography (CT) scans, doppler ultrasound, MAGiC, and dynamic contrast-enhanced (DCE)-MRI. The levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-ch), low-density lipoprotein cholesterol (LDL-ch), C-reactive protein (CRP), and procalcitonin (PCT) were also measured, and the National Institutes of Health Stroke Scale (NIHSS) was used to evaluate stroke severity. T2 and proton density (PD) values were markedly lower in severe patients than in mild-to-moderate patients, and the DCE-MRI Ktrans value was substantially higher in severe patients compared to mild-to-moderate patients. Furthermore, T2 and PD correlated negatively, while Ktrans correlated positively with CRP. Receiver operating characteristic (ROC) showed T2 and Ktrans to have the best diagnostic potential as MAGiC and DCE-MRI parameters, respectively. As such, combining T2 and Ktrans could improve severe stroke diagnosis accuracy. Moreover, TG, LDL-ch, CRP, T2, and Ktrans were independent risk factors for severe stroke. T2 and PD MAGiC parameters and the DCE-MRI Ktrans parameter could be used as indices to predict severe stroke, while combining T2 and Ktrans might provide better diagnostic accuracy.

Risk of Long-Term Ischemic Stroke in Patients With Traumatic Brain Injury and Incident Hypertension.

Traumatic brain injury (TBI) is independently associated with hypertension and ischemic stroke. The goal of this study was to determine the interplay between TBI and incident hypertension in the occurrence of post-TBI stroke. This prospective study used a hospital-based registry to identify patients without pre-existing comorbidities. TBI patients (n = 3664) were frequency matched on age, sex, and race to non-TBI patients (n = 1848). Follow-up started 6 months post-TBI or study entry and extended up to 10 years. To examine hypertension's role in post-TBI stroke, we used logistic regression models to calculate the effect estimates for stroke in four exposure categories that included TBI or hypertension in isolation and in combination. Second, we calculated the conditional direct effect (CDE) of TBI in models that considered hypertension as intermediary. Third, we examined whether TBI effect was modified by antihypertensive medication use. The 10-year cumulative incidence of stroke was higher in the TBI group (4.7%) than the non-TBI group (1.3%; p < 0.001). TBI patients who developed hypertension had the highest risk of stroke (odds ratio [OR] = 4.83, 95% confidence interval [CI] = 2.53-9.23, p < 0.001). The combined effect estimates were less than additive, suggesting an overlapping biological pathway. The total effect of TBI (OR = 3.16, 95% CI = 1.94-5.16, p < 0.001) was higher than the CDE that accounted for hypertension (OR = 2.45, 95% CI = 0.93-6.47, p = 0.06). Antihypertensives attenuated the TBI effect, suggesting that the TBI effect on stroke is partially mediated through hypertension. TBI is an independent risk factor for long-term stroke, and the underlying biological pathway may partly operate through TBI-precipitated hypertension. These findings suggest that screening for hypertension may mitigate stroke risk in TBI.

Atrial Fibrillation Burden: Impact on Stroke Risk and Beyond.

Atrial fibrillation (AF) is an important independent risk factor for stroke. Current guidelines handle AF as a binary entity with risk driven by the presence of clinical risk factors, which guides the decision to treat with an oral anticoagulant. Recent studies in the literature suggest a dose-response relationship between AF burden and stroke risk, in both clinical AF and subclinical atrial fibrillation (SCAF), which differs from current guidance to disregard burden and utilize clinical risk scores alone. Within clinical classification and at the same risk levels in various scores, the risk of stroke increases with AF burden. This opens the possibility of incorporating burden into risk profiles, which has already shown promise. Long-term rhythm monitoring is needed to elucidate SCAF in patients with stroke. Recent data from randomized trials are controversial regarding whether there is an independent risk from AF episodes with a duration of less than 24 h, including the duration of SCAF greater than six minutes but less than 24 h.

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

ObjectivesIncreased 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 MethodsDNA 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. ResultsThe 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). ConclusionsWe 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.

Nonalcoholic fatty liver disease is an independent risk factor for ischemic stroke after revascularization in patients with Moyamoya disease: a prospective cohort study

BackgroundThe study aimed to investigate the association between nonalcoholic fatty liver disease (NAFLD) and ischemic stroke events after revascularization in patients with Moyamoya disease (MMD).MethodsThis study prospectively enrolled 275 MMD patients from September 2020 to December 2021. Patients with alcoholism and other liver diseases were excluded. NAFLD was confirmed by CT imaging or abdominal ultrasonography. Stroke events and modified Rankin Scale (mRS) scores at the latest follow-up were compared between the two groups.ResultsA total of 275 patients were enrolled in the study, among which 65 were diagnosed with NAFLD. Univariate logistic regression analysis showed that NAFLD (P = 0.029) was related to stroke events. Multivariate logistic regression analysis showed that NAFLD is a predictor of postoperative stroke in MMD patients (OR = 27.145, 95% CI = 2.031–362.81, P = 0.013). Kaplan-Meier analysis showed that compared with MMD patients with NAFLD, patients in the control group had a longer stroke-free time (P = 0.004). Univariate Cox analysis showed that NAFLD (P = 0.016) was associated with ischemic stroke during follow-up in patients with MMD. Multivariate Cox analysis showed that NAFLD was an independent risk factor for stroke in patients with MMD (HR = 10.815, 95% CI = 1.259–92.881, P = 0.030). Furthermore, fewer patients in the NAFLD group had good neurologic status (mRS score ≤ 2) than the control group (P = 0.005).ConclusionNAFLD was an independent risk factor for stroke in patients with MMD after revascularization and worse neurological function outcomes.

Investigation of telomere length in young age ischemic stroke patients

Background &amp; Objective: Telomere length is frequently accepted as a marker of biological aging. Various studies examine the relationship between telomere length, accepted as a marker of biological aging, and stroke, but this relationship has not been clearly demonstrated. The objective of this study is to determine whether short DNA telomere length is an independent risk factor for stroke. Methods: Our study examined telomere length in young patients with ischemic stroke. The study included 60 patients with a history of ischemic stroke at a young age within the last 3 years and a control group consisting of 40 volunteers with similar age, gender, and disease history defined as risk factors for stroke. Results: In our study, the mean telomere length of the patient group was significantly higher than the mean telomere length of the control group. However, the telomere length of the patients in the study did not show a significant difference between socio-demographic and risk factors defined for ischemic stroke. Conclusion: Our study is very important in being the first to show such a relationship between telomere length and young age ischemic stroke. The low sample size may partially explain this result compared to other studies, as well as the study’s design, the study population’s age, ethnicity, and methods of studying telomere length. More studies with a larger sample size with younger patients are needed to better understand the relationship between telomere length and stroke in the future.

Bilateral nephrectomy impairs cardiovascular function and cerebral perfusion in a rat model of acute hemodilutional anemia.

Anemia and renal failure are independent risk factors for perioperative stroke, prompting us to assess the combined impact of acute hemodilutional anemia and bilateral nephrectomy (2Nx) on microvascular brain Po2 (PBro2) in a rat model. Changes in PBro2 (phosphorescence quenching) and cardiac output (CO, echocardiography) were measured in different groups of anesthetized Sprague-Dawley rats (1.5% isoflurane, n = 5-8/group) randomized to Sham 2Nx or 2Nx and subsequently exposed to acute hemodilutional anemia (50% estimated blood volume exchange with 6% hydroxyethyl starch) or time-based controls (no hemodilution). Outcomes were assessed by ANOVA with significance assigned at P < 0.05. At baseline, 2Nx rats demonstrated reduced CO (49.9 ± 9.4 vs. 66.3 ± 19.3 mL/min; P = 0.014) and PBro2 (21.1 ± 2.9 vs. 32.4 ± 3.1 mmHg; P < 0.001) relative to Sham 2Nx rats. Following hemodilution, 2Nx rats demonstrated a further decrease in PBro2 (15.0 ± 6.3 mmHg, P = 0.022). Hemodiluted 2Nx rats did not demonstrate a comparable increase in CO after hemodilution compared with Sham 2Nx (74.8 ± 22.4 vs. 108.9 ± 18.8 mL/min, P = 0.003) that likely contributed to the observed reduction in PBro2. This impaired CO response was associated with reduced fractional shortening (33 ± 9 vs. 51 ± 5%) and increased left ventricular end-systolic volume (156 ± 51 vs. 72 ± 15 µL, P < 0.001) suggestive of systolic dysfunction. By contrast, hemodiluted Sham 2Nx animals demonstrated a robust increase in CO and preserved PBro2. These data support the hypothesis that the kidney plays a central role in maintaining cerebral perfusion and initiating the adaptive increase in CO required to optimize PBro2 during acute anemia.NEW & NOTEWORTHY This study has demonstrated that bilateral nephrectomy acutely impaired cardiac output (CO) and microvascular brain Po2 (PBro2), at baseline. Following acute hemodilution, nephrectomy prevented the adaptive increase in CO associated with acute hemodilution leading to a further reduction in PBro2, accentuating the degree of cerebral tissue hypoxia. These data support a role for the kidney in maintaining PBro2 and initiating the increase in CO that optimized brain perfusion during acute anemia.

Epidemiology, prognosis, and challenges in the management of hyperthyroidism-related atrial fibrillation.

Atrial fibrillation (AF) is a common condition with a global estimated prevalence of 60 million cases, and the most common cardiac complication of hyperthyroidism, occurring in 5-15% of overtly hyperthyroid patients. Additionally, subclinical hyperthyroidism and high-normal free T4 have been associated with an increased risk in the development of AF. Hyperthyroidism-related AF is a reversible cause of AF, and the majority of patients spontaneously revert to sinus rhythm in 4-6 months during or after restoration of euthyroidism. Therefore, restoring thyroid function is an indispensable element in hyperthyroidism-related AF management. Rate control with beta-blockers consists another first-line therapy, reserving rhythm control in cases of persistent hyperthyroidism-related AF. It is still controversial whether hyperthyroidism is an independent risk factor of stroke in nonvalvular AF. As a result, initiating anticoagulation should be guided by the clinical thromboembolic risk score CHA2DS2-VASc score in the same way it is applied in patients with non-hyperthyroidism-related AF. Treatment with the novel direct oral anticoagulants appears to be as beneficial and may be safer than warfarin in patients with hyperthyroidism-related AF. In this review, we address the epidemiology, prognosis, and diagnosis of hyperthyroidism-related AF, and we discuss the management strategies and controversies in patients with hyperthyroidism-related AF.

Abstract TP292: Chronic Kidney Disease Exacerbates Post-Stroke Cell Death and Inflammatory Mechanisms

Chronic kidney disease (CKD) is an important independent risk factor for stroke. To understand the mechanisms of CKD that exacerbates stroke pathogenesis, we developed a rodent CKD model by feeding adult C57BL/6 mice with adenine. There was a gradual progression of CKD from mild to severe stages between days 7 and 28 identified by a combination of hematological (creatinine, blood urea nitrogen, and total protein) and imaging (MRI, μCT, dual-energy X-ray absorptiometry, and ultrasound) markers. The CKD cohort showed significant vascular fibrosis, collagen deposition, microvascular rarefaction, and tubulointerstitial abnormalities in the kidneys compared to the control. Induction of transient focal ischemia (by MCA occlusion) on day 28 of adenine treatment led to bigger infarcts (estimated by MRI on day 1 of reperfusion) and worsened motor function (assessed by rotarod test and beam walk test on days 1, 3, 7 and 14 of reperfusion) compared with non-CKD control cohort. The CKD group also showed twice higher mortality by day 14 of reperfusion after transient MCAO compared to control. Proteomic profiling showed that pro cell death and inflammatory mechanisms were directly induced in the brain by CKD pathogenesis. Overall, these studies conclude that CKD-induced cell death and inflammatory mechanisms in the brain contribute to severe and disabling stroke.

Abstract 19: Von Willebrand Factor Deficiency Improves Long Term Stroke Outcomes in Mice With Respiratory Infections

Background: Preceding respiratory tract infections (RTI) due to bacteria or virus has been linked to an increasing risk of stroke likely by potentiating an inflammatory immune response, endothelial dysfunction, platelet activation, and coagulopathy. Von Willebrand factor (VWF) plays a crucial role in hemostasis and thrombosis by promoting platelet adhesion to the subendothelial matrix and factor VIII stabilization. VWF activity is regulated by the protease ADAMTS13. Prior population-based studies suggest increased VWF levels and reduced ADAMTS13 activity as independent risk factors for stroke; however, a causal role of the VWF/ADAMTS13 axis in RTI-mediated stroke exacerbation is not investigated yet. Objective: To determine the causal role of the VWF/ADAMTS13 axis in a mouse model of preceding RTI and ischemic stroke. Methods: Wild-type (WT) mice were infected intranasally with sub-lethal doses of S. aureus or vehicle on days 0, 2, and 5. On day 6, infection was measured in the lungs (MRI), brain, and blood. VWF levels and ADTMTS13 activity were quantified by ELISA in the plasma on day 6 post-infection. In another set of experiments, on day 6 post-infection S. aureus -infected WT, Vwf -/- , Adamts13 -/- mice were subjected to transient (30 min) middle cerebral artery ischemia using a filament model. Functional outcomes (modified neurological severity score, rota-rod, corner, novel object recognition, and wire-hanging test) were measured in the same cohort of mice up to 4 weeks. Controls were mock-infected WT mice. Result: We demonstrate that a sustained S. aureus infection localized to lungs in WT mice, increases plasma VWF levels (~2-fold) and reduces ADAMTS13 activity that were associated with larger infarcts and worsened long-term functional outcomes (P&lt;0.05 vs. mock-infected mice). S. aureus infected VWF-deficient mice exhibited reduced infarcts and better long-term functional outcomes (P &lt;0.05 vs. S. aureus infected WT). In contrast, S. aureus infected ADAMTS13-deficient mice exhibited larger infarcts and worse long-term functional outcomes (P &lt;0.05 vs. S. aureus infected WT). Conclusion: In a model of respiratory tract infection during the week preceding stroke, VWF has a causal role in worsening stroke outcomes while ADAMTS13 is protective.

Abstract WP272: Insulin Resistance Estimated by Estimated Glucose Disposal Rate Predicts Outcomes in Acute Ischemic Stroke Patients

Background: Estimated glucose disposal rate (eGDR), a simple and noninvasive measure of insulin resistance, has been proven to be an independent risk factor for first-time stroke and all-cause mortality. In this study, we aimed to investigate the associations between eGDR and the stroke outcome in patients with first-time acute ischemic stroke (AIS). Methods: We included first-time AIS patients with available data on eGDR in the China National Stroke Registry III (CNSR-III), and divided the subjects into lower eGDR group (eGDR ≤6 mg/kg/min) and higher eGDR group (eGDR &gt;6 mg/kg/min). The primary outcome was excellent functional outcome (modified Rankin Scale score 0-1) at 3 months. Secondary outcomes included stroke recurrence and favorable functional outcome (modified Rankin Scale score 0-2) at 3 months, and functional outcome and combined vascular event at one year. Univariate and multivariate analyses were performed to evaluate the association between eGDR and outcomes. Results: A total of 6,271 patients with AIS were included in this study. The median values of eGDR in lower and higher eGDR group were 5.0mg/kg/min (interquartile range, 4.2-5.6) and 7.6mg/kg/min (interquartile range, 6.8-9.6), respectively. Patients with higher eGDR were significantly associated with higher incidence of excellent functional outcome (adjusted odds ratio, 1.24; 95% confidence interval, 1.06-1.45; P&lt;0.01) at 3 months and favorable (adjusted odds ratio, 1.55; 95% confidence interval, 1.24-1.93; P&lt;0.01) and excellent (adjusted odds ratio, 1.28; 95% confidence interval, 1.08-1.51; P&lt;0.01) functional outcome at one year. However, there was no significant difference in stroke recurrence between these two groups at 3 months (adjusted odds ratio, 0.81; 95% confidence interval, 0.61-1.06; P=0.12) and one year (adjusted odds ratio, 0.91; 95% confidence interval, 0.73-1.14; P=0.41). Conclusion: eGDR is a predictor of functional outcome in patients with AIS, independent of traditional cardiovascular predictors.

Risk factors for the development of cryptogenic stroke and the predictive value of right-to-left shunt in patent foramen ovale.

The purpose of this study was to evaluate the relationship between the right-to-left shunt of the patent foramen ovale and the risk score for paradoxical embolism in cryptogenic stroke, as well as the risk factors for the development of cryptogenic stroke. A retrospective analysis was performed on 257 patients with cryptogenic stroke who were diagnosed and treated in our hospital from February 2020 to January 2022 as a study group, and 98 patients who were diagnosed and treated at the Department of Neurology in our hospital at the same time and excluded from stroke, were selected as the control group. Transcranial Doppler ultrasound acoustic contrast testing was used to grade right-to-left shunts of patent foramen ovale. Clinical information of individuals who had cryptogenic strokes was examined. The correlation between the right-to-left shunt of patent foramen ovale and the risk score for both cryptogenic stroke and paradoxical embolism was analyzed. The factors affecting the occurrence of cryptogenic stroke were investigated. The correlation between right-to-left shunt and paradoxical embolism risk score was explored. Receiver operator characteristic curve (ROC) analysis was used to evaluate each factor's clinical usefulness in predicting the occurrence of cryptogenic stroke. No difference was observed in the history of hypertension, low-density lipoprotein, C-reactive protein and fibrinogen between the control group and the study group (p<0.05). In the study group with patent foramen ovale, the proportion of patients with grades I and II of the right-to-left shunt of patent foramen ovale was significantly lower than that in the control group, while the percentage of patients with grades III and IV was obviously greater than that in the control group (p<0.05). Right-to-left shunt grade, C-reactive protein, and fibrinogen were independent risk factors for cryptogenic stroke by logistic multivariate regression analysis (p<0.05). With an increase in the right-to-left shunt of the patent foramen ovale, patients' risk scores for paradoxical embolism increased considerably (p<0.05). In patients with cryptogenic stroke, the right-to-left shunt grade of the patent foramen ovale was positively connected with the paradoxical embolism risk score (r=0.331, p<0.001). ROC analysis results showed that the areas under the curves (AUC) of right-to-left shunt grading, C-reactive protein, and fibrinogen were 0.651, 0.871, and 0.779, respectively. The combination of the three indexes had an AUC of 0.908, a sensitivity of 87.90%, a specificity of 82.70%, and a Youden index of 0.706, indicating a high predictive value of the combination. The right-to-left shunt of patent foramen ovale was an independent risk factor for cryptogenic stroke, which was positively correlated with the paradoxical embolic risk score. Its combination with clinical serologic indexes had a high clinical value for predicting cryptogenic stroke.

Impact of Comorbid Sleep-Disordered Breathing and Atrial Fibrillation on the Long-Term Outcome After Ischemic Stroke.

Sleep-disordered breathing (SDB) and atrial fibrillation (AF) are highly prevalent in patients with stroke and are recognized as independent risk factors for stroke. Little is known about the impact of comorbid SDB and AF on long-term outcomes after stroke. In this prospective cohort study, 353 patients with acute ischemic stroke or transient ischemic attacks were analyzed. Patients were screened for SDB by respiratory polygraphy during acute hospitalization. Screening for AF was performed using a 7-day ECG up to 3× in the first 6 months. Follow-up visits were scheduled at 1, 3, 12, 24, and 36 months poststroke. Cox regression models adjusted for various factors (age, sex, body mass index, hypertension, diabetes, dyslipidemia, and heart failure) were used to assess the impact of comorbid SDB and AF on subsequent death or cerebro-cardiovascular events. Among 353 patients (299 ischemic stroke and 54 transient ischemic attacks), median age, 67 (interquartile range, 57-74) years with 63% males. Moderate-to-severe SDB (apnea-hypopnea index score, ≥15/h) was present in 118 (33.4%) patients. Among the 56 (15.9%) patients with AF, 28 had comorbid moderate-to-severe SDB and AF. Over 36 months, there were 12 deaths and 67 recurrent cerebro-cardiovascular events. Patients with comorbid moderate-to-severe SDB and AF had a higher risk of subsequent death or cerebro-cardiovascular events compared with those with only moderate-to-severe SDB without AF (hazard ratio, 2.49 [95% CI, 1.18-5.24]) and to those without moderate-to-severe SDB or AF (hazard ratio, 2.25 [95% CI, 1.12-4.50]). However, no significant difference was found between the comorbid moderate-to-severe SDB and AF group and the group with only AF without moderate-to-severe SDB (hazard ratio, 1.64 [95% CI, 0.62-4.36]). Comorbid moderate-to-severe SDB and AF significantly increase the risk of long-term mortality or recurrent cerebro-cardiovascular events after acute ischemic stroke. Considering both conditions as cumulative and modifiable cerebro-cardiovascular risk factors is of interest for the management of acute stroke. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02559739.

Association of systemic inflammatory response index and plaque characteristics with the severity and recurrence of cerebral ischemic events

AimWe aimed to investigate the relationship between systemic inflammatory response index (SIRI) and intracranial plaque features, as well as the risk factors related to the severity and recurrence of cerebral ischemic events. MethodsWe enrolled 170 patients with cerebral ischemic events. Baseline demographic characteristics and laboratory indicators were collected from all participants. All patients were assessed by high-resolution magnetic resonance vessel wall imaging for culprit plaque characteristics and intracranial atherosclerotic burden. Outpatient or telephone follow-up were conducted at 1, 3, and 6 months after discharge. ResultsSIRI levels were significantly associated with the enhanced plaque number (r = 0.205, p = 0.007), total plaque stenosis score (r = 0.178, p = 0.020), total plaque enhancement score (r = 0.222, p = 0.004), intraplaque hemorrhage (F = 5.630, p = 0.004), and plaque surface irregularity (F = 3.986, p = 0.021). Higher SIRI levels (OR = 1.892), total plaque enhancement score (OR = 1.392), intraplaque hemorrhage (OR = 3.370) and plaque surface irregularity (OR = 2.846) were independent risk factors for moderate-severe stroke, and these variables were significantly positively correlated with NIHSS (P < 0.05 for all). In addition, higher age (HR = 1.063, P = 0.015), higher SIRI levels (HR = 2.003, P < 0.001), and intraplaque hemorrhage (HR = 4.482, P = 0.008) were independently associated with recurrent stroke. ConclusionsHigher SIRI levels may have adverse effects on the vulnerability and burden of intracranial plaques, and links to the severity and recurrence of ischemic events. Therefore, SIRI may provide important supplementary information for evaluating intracranial plaque stability and risk stratification of patients.

Diabetes Mellitus among Patients with Acute Ischemic Stroke Admitted to the Department of Medicine in a Tertiary Care Center.

Diabetes mellitus is a major public health concern and a continuously growing chronic disease worldwide. Diabetes mellitus is one of the modifiable, independent, and major risk factors of ischemic stroke. This study aimed to find the prevalence of diabetes mellitus among patients with acute ischemic stroke admitted to the Department of Medicine in a tertiary care centre. This descriptive cross-sectional study was conducted among patients with acute ischemic stroke admitted to the Department of Medicine from 19 July 2023 to 19 November 2023 after obtaining ethical approval from the Institutional Review Committee. Detailed clinical history, random blood sugar and glycated haemoglobin were used to define diabetes mellitus. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Among 80 patients, diabetes mellitus was seen in 25 (31.25%) (21.09-41.41, 95% Confidence Interval). Among them, 19 (76%) had previously diagnosed and 6 (24%) had newly diagnosed diabetes mellitus. The poor glycemic control was seen in 11 (44%). The prevalence of diabetes mellitus among patients with acute ischemic stroke was found to be higher than in studies done in similar settings. diabetes mellitus; glycated hemoglobin; ischemic stroke.