Prestroke Use Research Articles

The impact of pre-stroke metformin use on clinical outcomes after acute ischemic stroke: A systematic review and meta-analysis

ObjectivesStroke is a leading cause of mortality and disability globally, with limited treatment options available for acute ischemic stroke (AIS) patients. Type 2 diabetes mellitus (T2DM) is not only widespread but also a known risk factor for stroke. Our meta-analysis aims to assess the influence of pre-stroke metformin use on the clinical outcomes in AIS patients with T2DM. Materials and MethodsWe conducted this study following PRISMA guidelines, searching the following databases: Medline, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials up to February 29, 2024. All studies providing separate data on AIS patients using metformin were included, and statistical analysis was conducted using R software to pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). ResultsOut of 1051 studies, 7 met the inclusion criteria for our meta-analysis with a total of 11589 diabetic patients, including 5445 patients taking metformin and 6144 diabetic patients in the non-metformin group. Compared to the non-metformin group, the metformin group had a significantly higher rate of mRS 0-2 score at discharge (OR 1.56; 95% CI 1.25:1.95; p=< 0.01) and a lower rate of 90-day mortality (OR 0.51; 95% CI 0.42:0.61; p=< 0.01), with no significant difference in sICH (OR 0.88; 95% CI 0.47:1.64; p= 0.68) between the two groups. ConclusionsOur meta-analysis demonstrated that pre-stroke metformin use is associated with higher functional independence and lower mortality in AIS patients with T2DM.

Abstract P281: Pre-Stroke Use of Dipeptidyl Peptidase-4 Inhibitors in Elderly Patients May Reduce Neurological Severity at the Onset of Stroke: A Retrospective Cohort Study

Introduction: Functional outcomes after acute stroke (AS) are related to the initial neurological severity. Therefore, neuroprotective agents to reduce initial brain damage at AS onset shows promise as a preventive approach. Dipeptidyl peptidase 4 inhibitors (DPP4i) have been reported to reduce stroke volume in mice. Therefore, DPP4i may exert neuroprotective effects on brain damage caused by AS. However, the association between pre-stroke use of DPP4i and neurological severity at the onset of AS has not been well studied. Hypothesis: Pre-stroke DPP4i use reduces neurological severity (NS) at the onset of AS. Methods: We conducted a retrospective cohort study involving patients admitted within 24 hours of AS onset between January 2013 and March 2019 with available pre-stroke medication information. We defined mild NS as a score of ≤5 points on the National Institutes of Health Stroke Scale. We used logistic regression analysis using variables for pre-stroke DPP4i initiation, calculated propensity scores for pre-stroke DPP4i use and implemented one-to-one propensity score matching (PSM). We compared the incidence of mild NS between the two groups. Results: Out of 4294 patients with AS, 3472 met the inclusion criteria. After PSM, we had 221 patients in each group. The median ages of DPP4i users and non-users were 79 and 78 years, respectively. Among the 221 DPP4i users and the 221 non-users, 140 (63.4%) and 121 (54.8%) patients had reduced NS, respectively (p=0.0659 by chi-square test, standardized difference=0.1756). The chi-square test did not show a significant difference in the matched cohort, but the standardized difference of 0.1 or more suggested that the two groups were not balanced on the incidence of mild NS. Conclusions: The pre-stroke use of DPP4i among elderly patients was associated with mild NS at AS onset, suggesting a potential neuroprotective effect of DPP4i on initial brain damage caused by AS. Further prospective studies with larger sample size are needed to verify the causal relationship between pre-stroke DPP4i use and NS at AS onset.

Abstract P418: Pre-Stroke Use of Loop Diuretics in Elderly Patients Aggravates Renal Function at the Onset of Acute Stroke: A Propensity Score-Matched, Retrospective Cohort Study

Introduction: Renal function is often impaired in elderly patients experiencing acute stroke (AS) due to pre-existing chronic kidney disease (CKD), which can progress to severe renal dysfunction (SRD). SRD can limit pharmacological treatments, such as anticoagulants, antiplatelets, diabetes medicines, or antihypertensives during the AS phase. Therefore, preventing CKD progression to SRD and minimizing the use of renal-impairing agents before SRD development is crucial. Loop diuretics, commonly prescribed for heart failure, have been reported to exacerbate renal function. Sex-based differences in renal function due to gonadal hormones exist. However, the impact of loop diuretics on the risk of SRD before AS in both sexes remains unclear. Hypothesis: The pre-stroke use of loop diuretics in elderly patients aggravates renal function at the onset of AS in both sexes. Methods: We conducted a propensity score-matched, retrospective cohort study involving patients admitted within 24 hours of AS onset between January 2013 and March 2019 with available pre-stroke medication information. We defined SRD as a calculated creatinine clearance (Ccr) of &lt;30 ml/min. We analyzed logistic regression using variables for pre-stroke loop diuretics initiation, calculated propensity scores for pre-stroke loop diuretics usage, and implemented a one-to-one propensity score matching (PSM) by sex. We compared the incidence of SRD between loop diuretics users and non-users within each sex group. Results: Among 4294 patients with AS, 3472 met the inclusion criteria. Among these, 129 male and 143 female loop diuretic users were matched with non-users using the one-to-one PSM. After the PSM, median ages were 80 years in males and 86 years in females, respectively. The SRD incidence was 38.0% (49/129) versus 16.8% (21/129) in males (p&lt;0.0001) and 50.4% (78/143) versus 23.1% (48/143) in females (p&lt;0.0001), comparing users to non-users. Conclusions: The pre-stroke use of loop diuretics in elderly patients may increase the risk of SRD at the onset of AS in both sexes. Therefore, cautious utilization of loop diuretics in elderly patients is recommended to prevent SRD before AS. A possible option is to switch loop diuretics to other medications, which have been shown to have better renal protective effects. Further prospective studies are needed to validate our findings and establish the appropriate usage of loop diuretics in elderly patients before AS.

Abstract TMP98: Pre-Stroke Use of Blood-Brain Barrier Crossing Angiotensin Receptor Blockers in Elderly Patients Mitigates Neurological Severity at the Onset of Acute Stroke

Introduction: Functional outcomes after acute stroke (AS) are related to the initial neurological severity. Therefore, using neuroprotective agents to prevent or reduce brain damage shows promise as a preventive approach. Blood-brain barrier crossing (BBBc) angiotensin receptor blockers (ARBs) have been reported to reduce the risk of cognitive disorders. Therefore, BBBc ARBs may exert neuroprotective effects on brain damage caused by AS. However, the association between pre-stroke BBBc ARB use and neurological severity at the onset of AS has not been well studied. Hypothesis: Pre-stroke BBBc ARBs in elderly patients is linked to mild neurological severity (MNS) at the time of AS onset. Methods: We retrospectively included patients admitted within 24 hours of AS onset between January 2013 and March 2019 with available pre-stroke medication information. We defined MNS as a score of ≤5 points on the National Institutes of Health Stroke Scale. We conducted logistic regression analysis using variables for pre-stroke BBBc ARBs initiation, calculated propensity scores for pre-stroke BBBc ARBs use, and implemented one-to-one propensity score matching (PSM). The McNemar test assessed whether pre-stroke BBBc ARBs administration significantly affected MNS. Results: Out of 4294 patients with AS, 3472 met the inclusion criteria. Following one-to-one PSM, we identified 508 patients each in the BBBc ARBs usage and non-usage groups. The median ages of BBBc ARBs users and non-users were 80 and 81 years, respectively. Among the 508 BBBc ARBs users and the 508 non-users, 325 and 278 patients exhibited MNS, respectively (p=0.0027). Furthermore, the McNemar test revealed an asymmetrical binary matched pairs contingency table of MNS (p=0.0021), indicating a significant association between pre-stroke BBBc ARB use and MNS at the time of AS onset. Conclusions: The pre-stroke utilization of BBBc ARBs among elderly patients is associated with MNS at the onset of AS, implying potential neuroprotective effects against AS-induced brain damage. Further prospective studies are warranted to validate our findings and establish the practical application of BBBc ARBs for neuroprotection before AS.

Abstract 124: Pre-Stroke Aspirin Use Does Not Impact Small Subcortical Stroke Size: A Secondary Analysis of the SPS3 Trial

Introduction: The use of pre-stroke aspirin is associated with smaller stroke size in first-time stroke related to large vessel occlusion. However, it is unknown whether pre-stroke aspirin use impacts stroke size for an acute small subcortical infarct (SSI). We hypothesized that pre-stroke aspirin use would be associated with a smaller sized SSI. Methods: We performed a secondary analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) dataset which enrolled between 2003 and 2007. We included participants ≥ 55 years old with brain-MRI confirmed SSI being ≤ 20 mm in maximal diameter on diffusion weighted imaging. Stroke size was determined retrospectively by the study team on the index event brain MRI. Pre-stroke medications were recorded at the time of enrollment. Chi-squared and student’s T test were used for categorical and continuous variables, respectively. Binary logistic regression models were fitted for likelihood ratios. Results: Of the 3020 participants enrolled in SPS3, a total of 2183 met inclusion criteria: 663 with pre-stroke aspirin monotherapy and 1520 without pre-stroke antithrombotic use, Table 1. Those with aspirin use were older with a higher incidence of diagnoses of hypertension, hyperlipidemia, and diabetes mellitus, though otherwise sex, and tobacco use did not differ. The mean maximal stroke width, trended towards, but was not statistically impacted by pre-stroke aspirin use [pre-stroke aspirin: 11.8 (4.1) mm vs 11.4 (4.1) mm, p =0.065]. After adjustment for significant variables, pre-stroke aspirin use did not impact the odds of a larger infarct size (OR 0.779, 95%CI 0.615-1.04, p =0.092). Conclusion: Despite those with pre-stroke aspirin use having more vascular risk factors, its use did not impact stroke size amongst those with an acute SSI enrolled in the SPS3 trial.

Abstract 59: Contemporarypre-Stroke Antiplatelet Use and the Risk of Symptomatic Hemorrhagic Transformation After Intravenous Thrombolysis

Introduction: Many patients are taking antiplatelet medications when an acute stroke occurs. We evaluated the risk of hemorrhage associated with newer, more potent antiplatelet medications and dual antiplatelet regimens among patients treated with intravenous tissue plasminogen activator (IV-tPA). Methods: Using the American Heart Association Get With The Guidelines-Stroke Registry from January 1, 2013 to December, 31 2021, we analyzed data on all ischemic stroke patients hospitalized and treated with IV-tPA. The exposure of interest was pre-stroke antiplatelet use categorized as none, single (SAPT), and dual antiplatelet therapy (DAPT). The primary outcome of interest was symptomatic intracranial hemorrhage (sICH) within 36 hours of tPA administration. A secondary outcome was modified Rankin Scale (mRS) at discharge. Propensity score matching was performed to mitigate confounding by indication for each pre-stroke antiplatelet treatment strategy. Adjusted multivariate logistic regression analyses were performed to evaluate associations between pre-stroke antiplatelet medication and outcomes of interest. Results: The analytic cohort included 320,493 patients who had an acute ischemic stroke and received IV-tPA. The pre-stroke antiplatelet therapy utilization frequencies were 56.9% no antiplatelet, 36.7% SAPT, and 6.4% DAPT. The frequency of sICH was 2.9%, 3.8%, and 4.1% among patients treated with none, SAPT, and DAPT respectively (p&lt;0.001). After performing propensity score matching, both SAPT (OR 1.13, 95% C.I. 1.08-1.20) and DAPT (OR 1.28, 95% C.I. 1.14-1.43) were associated with increased risks of sICH. DAPT was also associated with a significantly higher risk of sICH compared with SAPT (OR 1.18, 95% C.I. 1.08-1.28). Use of pre-stroke antiplatelet medications was associated with lower odds of discharge mRS &lt; 2 compared to none: (SAPT OR 0.92, 95% C.I. 0.89-0.96; DAPT OR 0.93, 95% C.I. 0.87-0.98). Conclusion: In this study, pre-stroke antiplatelet use was associated with a modest, dose-dependent risk of sICH and functional dependence.

Abstract WP5: Outcomes of Pre-Stroke Use of Metformin in Acute Ischemic Stroke Patients With Diabetes Mellitus: A Systematic Review and Meta-Analysis

Background: Diabetes mellitus (DM) is one of the risk factors for acute ischemic stroke, usually leading to poor prognosis. While DM can reduce the effect of intravenous thrombolysis, metformin can have a positive outcome on AIS patients. The outcomes of stroke in diabetic patients receiving metformin is largely unexplored. In the present study we performed a systematic review to assess the effect of metformin on AIS outcomes in diabetic patients. Methods: A systematic review of literature was performed following PRISMA guideline. PubMed, Embase, Scopus and Web of science were used for the literature search. Study outcomes such as modified Rankin Scale (mRS 0-2) at discharge, symptomatic intracranial hemorrhage (sICH) and 90-day mortality were extracted from the full text and analysis were performed to calculate 95% confidence intervals with pooled odds ratio for all the outcomes. Results: Total of six studies were included in the analysis with a total of 5390 patients taking metformin and 6039 patients without metformin. Favorable mRS of 0-2 was significantly higher among patients taking metformin (OR 1.52, 95% CI 1.21:1.93). The mortality rate was significantly lower in metformin group (OR 0.51, 95% CI 0.42:0.61). These results favor the beneficial effect of taking metformin among DM patients with AIS. Conclusion: Overall, chronic use of metformin seems to be beneficial in AIS patients with DM. There is a trend of favorable outcomes of mRS and Mortality, with a non-statistical significance increase of sICH.

The impact of pre-stroke aspirin exposure on radiographic appearance and disability outcomes: A post-hoc analysis of the SPS3 trial: Aspirin Use and Small Subcortical Stroke

ObjectivesThe effect of pre-stroke use of aspirin on small subcortical infarct dimensions or outcomes is not well described. We aimed to bridge this knowledge gap amongst a well-described and heterogeneous patient population. Materials and MethodsWe performed a post-hoc analysis of the Secondary Prevention of Small Subcortical Stroke (SPS3) trial. The primary exposure was aspirin use ≤7 days of index stroke. The primary outcomes were infarct dimensions. Functional outcomes by modified Rankin Scale (mRS) was a secondary outcome. Age restricted (≥55 years) subgroup analyses were performed as a sensitivity analysis. Descriptive statistical and regression modeling were performed for data analysis. ResultsWe included 1423 participants of which 453(31.8 %) used aspirin. Aspirin use was associated with more cardiovascular risk diagnoses. Maximal infarct diameter did not differ with pre-stroke aspirin use (11.3±4.2 mm versus 11.8±4.1 mm, p=0.057) however infarct area was smaller with exposure (126.4±90.0 mm2 versus 137.4±97.0 mm2, p=0.037) regardless of aspirin strength. Participants ≥55 years had smaller infarct diameters (11.1±4.2 mm versus 11.9±4.4 mm, p=0.019) and area (123.4±87.1 mm2 versus 130.6±93.2 mm2, p=0.037) with aspirin use. mRS did not significantly differ in our analyses. ConclusionsIn this post-hoc analysis of the SPS3 trial, pre-stroke aspirin use was associated with a smaller infarct area regardless of aspirin strength and without impact on functional outcomes. These findings were more pronounced in participants ≥55 years. Registrationhttps://clinicaltrials.gov/study/NCT00059306?term= %22sps3 %22&rank=1

Effect of pre-stroke antiplatelet use on stroke outcomes in acute small vessel occlusion stroke with moderate to severe white matter burden

BackgroundCerebral small vessel disease is characterized by white matter hyperintensities (WMH) and acute small vessel occlusion (SVO) stroke. We investigated the effect of prior antiplatelet use (APU) on stroke outcome in 1151 patients with acute SVO stroke patients and moderate to severe WMH. MethodsUsing a multicenter database, this retrospective study used quantitative WMH volume measurements and propensity score matching (PSM) for comparisons between patients with prior APU and without APU. Primary outcomes were stroke progression and poor functional outcome (modified Rankin Scale>2) at 3 months. Logistic regression analyses assessed associations between prior APU, WMH burden, and stroke outcomes. ResultsStroke progression was lower in the prior APU group in both the total cohort (14.8% vs. 6.9%, p < 0.001) and the PSM cohort (16.3% vs. 6.9%, p < 0.001). The proportion of poor functional outcomes at 3 months was not significantly different in the total cohort, but the PSM cohort showed a lower proportion in the prior APU group (30.8% vs. 20.2%, p = 0.002). Logistic regression analysis confirmed that prior APU was associated with a reduced risk of stroke progression (OR, 0.39; 95% CI, 0.22–0.70; p = 0.001) and poor functional outcome at 3 months (OR, 0.37; 95% CI, 0.23–0.59; p < 0.001). ConclusionPrior APU is associated with reduced stroke progression and improved functional outcome at 3 months in acute SVO stroke patients with moderate to severe WMH. Early treatment of WMH and acute SVO stroke may have potential benefits in improving stroke outcomes.

Undiagnosed major risk factors in acute ischaemic stroke patients: frequency, profile, stroke mechanisms and outcome.

There is scarce clinical information about the clinical profile of patients with acute ischaemic stroke with previously undiagnosed major vascular risk factors (UMRFs). This was a retrospective analysis of data from the Acute Stroke Registry and Analysis of Lausanne registry between 2003 and 2018 with univariate and multivariate logistic regression analyses comparing clinical profiles of patients with UMRFs to patients with at least one previously diagnosed MRF (DMRF). In all, 4354 patients (median age 70 years [interquartile range 15.2], 44.7% female) were included after excluding 763 (14.9%) for lack of consent and three for missing information. Amongst 1125 (25.8%) UMRF patients, 69.7% (n = 784) had at least one newly diagnosed MRF and the others none. The newly detected MRFs were dyslipidaemia (61.4%), hypertension (23.7%), atrial fibrillation (10.2%), diabetes mellitus (5.2%), ejection fraction <35% (2.0%) and coronary disease (1.0%). Comparing UMRF patients to DMRF patients, multivariate analysis showed a positive association with lower age, non-Caucasian ethnicity, contraceptive use (<55 years old), smoking (≥55 years old) and patent-foramen-ovale-related stroke mechanism. A negative association was found with pre-stroke antiplatelet use and higher body mass index. Functional outcome did not differ. Cerebrovascular recurrences were similar between groups. In this large single-centre cohort, 69.7% of patients with acute ischaemic stroke and UMRF were newly diagnosed with at least one new MRF, the most common being dyslipidaemia, hypertension or atrial fibrillation. Patients of the UMRF group were younger, more often smokers and on contraceptives, and had more patent-foramen-ovale-related strokes.

Symptomatic Intracranial Hemorrhage after Ischemic Stroke Treated with Bridging Revascularization Therapy.

(1) Background: bridging revascularization therapy is now the standard of care in patients with ischemic stroke due to large vessel occlusion. This study aimed to determine the frequency of symptomatic intracranial hemorrhage (sICH) related to this treatment, and to assess contributing factors and patients' outcomes. (2) Methods: consecutive ischemic stroke patients treated with bridging therapy were prospectively enrolled. sICH (intracranial hemorrhage with an increase in NIHSS score of ≥4 points) was assessed on imaging at 24 h. The functional status of patients was measured at 6 months using the mRS score; (3) Results: 176 patients were included (mean age 68.7 ± 1.2 years, 52.3% women), among whom 15 (8.5%) had sICH. Patients with sICH had more frequent alcohol abuse (30.1% versus 9.7%, p = 0.023), prestroke use of dual antiplatelet therapy (14.3% versus 1.3%, p = 0.002), higher NIHSS scores at admission (median score 20.5 versus 15, p = 0.01), greater systolic blood pressure upon admission, more frequent vascular intracranial calcifications (p = 0.004), leukoaraiosis (p = 0.001), and intracranial atheroma (p = 0.02), and higher neutrophil-to-lymphocyte ratios (p = 0.02) and neutrophil-to-platelet ratios (p = 0.04). At 6-month follow-up, 9 (60%) patients with sICH died, versus 18% of patients without sICH (p < 0.001). Only 1 (7%) patient with sICH had a good functional outcome, defined as an mRS score of 0 to 2, versus 51% of patients without sICH. (4) Conclusions: one in twelve ischemic stroke patients treated with bridging therapy suffered sICH. Given the observed poor outcomes after sICH, further studies are required to better identify patients at risk to help clinicians in guiding therapeutic strategies.

Abstract P598: Highly Purified Eicosapentaenoic Acid Use Can Reduce Neurological Severity at the Onset of Ischemic Stroke in Patients With Hyperlipidemia

Introduction: Functional outcomes after acute ischemic stroke (AIS) are related to initial neurological severity (NS). Therefore, neuroprotective drugs against ischemic injury are promising. Not only statins but also eicosapentaenoic acid (EPA) have neuroprotective effects. Hypothesis: Highly purified EPA (hp-EPA) pre-stroke may reduce NS at the onset of AIS. Methods: We retrospectively included patients with AIS and hyperlipidemia admitted to our institution between July 2012 and March 2019 from the prospectively and consecutively enrolled institutional stroke registry database. Hyperlipidemia was defined as serum values of low-density lipoprotein cholesterol (LDL-C) at arrival ≥140 mg/dl or triglycerides ≥150 mg/dl. We excluded patients: (1) admitted to our institution 24 h after AIS onset, (2) who did not stay in the hospital, and (3) in whom dyslipidemia drugs pre-stroke except the hp-EPA were administered. We collected data on age; sex; pre-stroke statin use, antiplatelets, anticoagulants, antihypertensives, and antidiabetic drugs; serum albumin, glucose, glycated hemoglobin (HbA1c), cholesterol, triglycerides, and c-reactive protein levels; pre-stroke modified Rankin scale and the National Institutes of Health Stroke Scale (NIHSS) scores; stroke subtypes at admission; hospitalizations; and home discharge. We performed a multivariable linear regression analysis to identify significant variables of NIHSS scores at arrival. Results: Of the 2,199 patients with AIS and hyperlipidemia during the study period, 691 met our inclusion and exclusion criteria, their median age was 75 years, and 18 (2.6%) received pre-stroke hp-EPA. In patients with and without pre-stroke EPA use, the median NIHSS scores were one and three, respectively. Multivariable regression analysis showed that the glucose, mRS, age, LDL-C, and anticoagulants increased the NIHSS score, albumin, HbA1c, high-density lipoprotein cholesterol, antihypertensives, antidiabetic drugs, and hp-EPA use decreased the NIHSS score. Conclusion Pre-stroke hp-EPA use reduced NS at the AIS onset in patients with hyperlipidemia and without other dyslipidemia drugs.

Impact of Preexisting Alcohol Use Disorder, Bipolar Disorder, and Schizophrenia on Ischemic Stroke Risk and Severity: A Lebanese Case-Control Study

Stroke remains a major leading cause of morbidity and death globally. For ischemic stroke, the most frequent type of stroke, there are numerous risk models and risk assessments offered. Further research into potential risk factors or triggers is being sought to improve stroke risk models. Schizophrenia, bipolar disorder, and alcohol use disorder are all common causes of serious mental illnesses in the general population. Due to the tangled relationship between stroke and many chronic illnesses, lifestyle factors, and diet that may be present in a patient with a mental disease, the relationship between mental diseases and stroke requires further validation. Consequently, the purpose of this study is to assess the potential influence of bipolar disorder, schizophrenia, and alcohol use disorder on stroke patients as compared to non-stroke participants, after controlling for demographic, physical, and medical conditions. We aimed, as a secondary objective, to evaluate the impact of these pre-existing disorders on stroke severity levels. This research is a case-control survey study involving 113 Lebanese patients with a clinical diagnosis of ischemic stroke and 451 gender-matched volunteers without clinical signs of stroke as controls recruited from several hospitals in Lebanon (April 2020-April 2021). Based on the participant's consent, data was collected by filling out an anonymous paper-based questionnaire. All of the odds ratios (ORs) generated by our regression model were greater than 1, indicating that the factors studied were associated with an increased risk of ischemic stroke. As such having schizophrenia (adjusted OR [aOR]: 6.162, 95% confidence interval [CI]: 1.136-33.423), bipolar disorder (aOR: 4.653, 95% CI: 1.214-17.834), alcohol use disorder (aOR: 3.918, 95% CI: 1.584-9.689), atrial fibrillation (aOR: 2.415, 95% CI: 1.235-4.721), diabetes (aOR: 1.865, 95% CI: 1.117-3.115), heart diseases (aOR: 9.890, 95% CI: 5.099-19.184), and asthma-COPD (aOR: 1.971, 95% CI: 1.190-3.263) were all involved with a high risk of developing an ischemic stroke. Moreover, obesity (aOR: 1.732, 95% CI: 1.049-2.861) and vigorous physical activity (aOR: 4.614, 95% CI: 2.669-7.978) were also linked to an increased risk of stroke. Moreover, our multinomial regression model revealed that the odds of moderate to severe/severe stroke were significantly higher in people with pre-stroke alcohol use disorder (aOR: 1.719, 95% CI: 1.385-2.133), bipolar disorder (aOR: 1.656, 95% CI: 1.281-2.141), and schizophrenia (aOR: 6.884, 95% CI: 3.294-11.492) compared to people who had never had a stroke. The findings in our study suggest that individuals with schizophrenia, bipolar disorder, and alcohol use disorder may be at a higher risk for ischemic stroke and exhibit more severe symptoms. We believe that the first step toward creating beneficial preventative and treatment interventions is determining individuals with schizophrenia, bipolar disorder, or alcohol use disorder, assessing their risk of ischemic stroke, developing more integrated treatments, and closely monitoring the long-term outcome in the event of an ischemic stroke.

Abstract TP171: Impacts Of Left Atrial Size On The Short-term And Long-term Outcomes After Acute Ischemic Stroke

Objectives: To investigate whether the left atrial diameter (LAD) was associated with stroke severity, outcome, long-term risk of stroke recurrence and mortality in patients with acute ischemic stroke. Methods: This study included acute ischemic stroke patients in the National Taiwan University Hospital Stroke Registry from 2015 to 2021. LAD was measured by transthoracic echocardiography and was divided by body surface area (indexed LAD) for standardization. Patients were further classified into normal (&lt;2.3 cm/m 2 ), mildly (2.4-2.6), moderately (2.7-2.9), and severely (≥3.0) abnormal LAD. Short- term outcomes included stroke severity, stroke-in-evolution, and 3-month modified Rankin Scale (mRS), while long-term outcomes include recurrent ischemic stroke and mortality. Results: In total, 3952 patients (mean age 69.7±14.1, 43% female) were enrolled. The mean indexed LAD was 2.3±0.6 cm/m 2 . Patients in the abnormal LAD groups were older, had more female, higher NIHSS, more cardioembolic stroke, more likely to received reperfusion therapy, had higher proportion of stroke-in-evolution and higher 3-month mRS. In adjusted analyses, increased indexed LAD (per 1 cm/m 2 ) was associated with functional independence (mRS 0-2) at 3 months (odds ratio (OR) 1.59, 95% CI 1.28-1.98). During the follow-up of 3.12±2.16 years, 413 patients had recurrent ischemic stroke and 747 patients died. Increased indexed LAD was associated with mortality (hazard ratio (HR) 1.21, 95% CI 1.04-1.40), but not recurrent ischemic stroke (HR 1.07, 95% CI 0.86-1.32). In the cryptogenic stroke subgroup, severely abnormal LAD was associated with recurrent ischemic stroke (HR 2.69, 95% CI 1.23-5.88). In the AF subgroup, patients with pre-stroke oral anticoagulant use had larger indexed LAD (2.9±0.6 vs 2.6±0.6), but they had lower initial NIHSS at (8 vs 10) and were more likely to achieve functional independence (OR 1.55, 95% CI 1.08-2.24). Conclusion: In patients with acute ischemic stroke, left atrial enlargement is associated with higher probability of functional independence at 3 months, but higher risk of long-term mortality. Despite having larger left atrial size, pre-stroke oral anticoagulant use might be associated with better outcome in patients with atrial fibrillation.

Pre-Stroke Statin Use Is Associated with Mild Neurological Deficits at the Onset of Acute Ischemic Stroke.

Pre-stroke statin use reduces infarct size. Therefore, this retrospective study aimed to investigate whether pre-stroke statin use is associated with mild neurological deficits (mND) at the onset of acute ischemic stroke (AIS). We included patients with AIS admitted to our institution within 24 h of stroke onset between 2011 and 2019. We collected data on age, sex, pre-stroke use of statins, the National Institutes of Health Stroke Scale (NIHSS) score, the serum biomarker levels, and stroke subtypes at admission. In addition, we defined mND as an NIHSS score ≤3 points. We conducted a logistic regression analysis using variables for pre-stroke statin initiation, calculated the propensity scores for pre-stroke statin use, and implemented propensity score matching (PSM). Finally, we used the McNemar test to evaluate whether pre-stroke statin administration significantly affected mND. Of 4370 patients, 2615 met our inclusion criteria. Among the 594 patients with pre-stroke statin use, 308 presented with mND. After PSM, 555 patients received pre-stroke statin treatment, while 286 patients with pre-stroke statin use presented with mND at admission (p = 0.0411). The binary matched pairs contingency table of mND was not symmetrical (p = 0.0385). Pre-stroke statin use is thus associated with mND at the onset of AIS.

Abstract 9448: Pre-Stroke Statin Use is Associated With Mild Neurological Symptoms at the Onset of Acute Ischemic Stroke

Introduction: Statins have protective effects against ischemic injury, and pre-stroke statin use augments cerebral blood flow, reduces infarct size, and improves neurological function in mice. Hypothesis: Pre-stroke statin is associated with mild neurological symptoms at the onset of acute ischemic stroke (AIS). Methods: We retrospectively included patients with AIS admitted to our institution within 24 hours of onset between April 2011 and March 2019. We collected data on age, sex, pre-stroke use of stains, antiplatelets, anticoagulants, antihypertensive drugs, and diabetes drugs, the National Institutes of Health Stroke Scale (NIHSS) score, serum levels of albumin, glucose, glycated hemoglobin, lipids, and c-reactive protein, and stroke subtypes at admission. In addition, we defined mild neurological symptoms (mNS) as the NIHSS score of three or less. We compared variables between patients with and without pre-stroke statins and identified variables with significant differences between them. We conducted a logistic regression analysis using variables for pre-stroke statin use except for the NIHSS score, mNS, lipids, or stroke subtypes, calculated propensity scores for a pre-stroke statin and implemented a one-to-one propensity score matching (PSM). We evaluated differences between matched pairs and whether pre-stroke statin was significant for mNS at admission. We used the McNemar test to evaluate symmetry on a binary matched pairs contingency table of mNS. Results: Two thousand six hundred fifteen patients met our inclusion criteria during the study period. In 594 patients (22.7%) with pre-stroke statins and 2021 patients without them, 308 (51.9%) and 895 (44.3%) patients presented mNS (p=0.0012). After one-to-one PSM, 555 patients underwent pre-stroke statin treatment, and 555 patients did not undergo it. There were no differences in variables between matched pairs except for the NIHSS score, mNS, or cholesterol levels; 286 patients with pre-stroke stains and 252 patients without them presented mNS at admission (p=0.0411), and the binary matched pairs contingency table of mNS was not symmetrical (p=0.0385). Conclusions: Pre-stroke statin use is associated with mNS at the onset of AIS.

Cardiovascular medications and long-term mortality among stroke survivors in the Brazilian Study of Stroke Mortality and Morbidity (EMMA).

To investigate the association between medication use and long-term all-cause mortality in a Brazilian stroke cohort. Both ischemic and hemorrhagic stroke were evaluated. Medication use was assessed as: never, only pre-stroke, only post-stroke, and continuous use. We evaluated anti-hypertensives, anti-diabetics, lipid-lowering drugs, anti-platelets, and anti-coagulants. Cox regression models were adjusted for sociodemographic and cardiovascular risk factors. Among 1173 incident stroke cases (median age: 68; 86.8% were ischemic, 70% first-ever stroke), medication use was low (overall: 17.5% pre-stroke, 26.4% post-stroke, and 40% were under continuous use). Anti-hypertensives and anti-platelets (aspirin) were the continuous cardiovascular medications used most often, at 83.5% and 72%, respectively, while statins (39.7%) and anti-diabetics (31.3%) were the least used. Medication use (pre-stroke, post-stroke and continuous use) was associated with a reduction in all-cause mortality risk, particularly among those under continuous use (multivariable hazard ratio, 0.52; 95% confidence interval (CI), 0.46-0.66) compared with never-users. Among ischemic stroke patients, this effect was similar (multivariable hazard ratio, 0.52; 95% CI, 0.40-0.68). No significant associations were evident among hemorrhagic stroke patients. The risk of all-cause mortality was reduced by 48% among those with ischemic stroke under continuous use of medications. Secondary prevention should be emphasized more strongly in clinical practice. Geriatr Gerontol Int 2022; 22: 715-722.

Effect of metformin on outcome after acute ischemic stroke in patients with type 2 diabetes mellitus

IntroductionDiabetes mellitus is a well-known risk factor for ischemic stroke and is associated with unfavorable outcome after stroke. Metformin is recommended as first-line treatment in these patients. Pre-stroke metformin use might have neuroprotective properties resulting in reduced stroke severity. However, results of the effects of pre-stroke metformin use on functional outcome are conflicting and has not been previously described in patients with type 2 diabetes mellitus regardless of stroke severity or revascularization treatment. In this study, we aimed to assess the association between metformin use and functional outcome in patients with type 2 diabetes mellitus and acute ischemic stroke. MethodsWe used data from patients with known type 2 diabetes mellitus who were admitted with acute ischemic stroke between 2017 and 2021 in the Isala Hospital Zwolle and Medisch Spectrum Twente (MST) Enschede, the Netherlands. The association between pre-stroke metformin use and favorable functional outcome at 3 months (defined as modified Rankin Scale (mRS) < 3) was expressed as Odds Ratios (ORs) with corresponding confidence intervals (CIs). Adjustments were made for age, sex, hyperglycemia on admission and revascularization treatment by means of multiple logistic regression. ResultsNine hundred thirty seven patients were included of whom 592 patients (63%) used metformin. Six hundred seventy eight (74%) patients were hyperglycemic on admission. Median mRS was 3 (IQR 2–6) and 593 patients (63%) had a favorable outcome. Pre-stroke metformin use was associated with favorable outcome (aOR of 1.94 (95%- CI 1.45–2.59)). ConclusionIn this study, we showed that pre-stroke metformin use was associated with favorable outcome after acute ischemic stroke in patients with diabetes mellitus type 2.

REHABILITATION RESULTS OF PATIENTS WITH COVID-19 RELATED STROKE

The aim of the study is to examine the patients with COVID-19 associated stroke who were admitted to the inpatient rehabilitation program in terms of clinical features, ambulation level and functional status, and to reveal the improvements achieved as a result of rehabilitation. 29 COVID-19-related stroke patients (group 1) and 29 non-COVID-19 stroke patients (group 2) were included in this study. The groups were compared in terms of demographic and clinical characteristics, risk factors, post-stroke disorders and complications of stroke. Motor function was evaluated with the Brunnstrom Motor Recovery Staging (BMRS), ambulation status was evaluated with the Functional Ambulation Scale (FAS), and functional disability was evaluated with the Functional Independence Scale (FIM). Both groups of patients were compared in terms of pretreatment and posttreatment values of BMRS, FIM and FAS stages. In addition, the changes in BMRS, FIM and FAS values within the group were evaluated. Pulmonary involvement (mild/moderate-severe) and the use of anticoagulants after COVID-19 infection were investigated in patients with COVID 19 stroke. In patients with COVID-19-associated stroke, the mean age was statistically significantly lower (p=0.045), the risk factor hypertension was significantly less (p=0.016), pre-stroke anticoagulant use was significantly higher (p=0.004), and deep vein thrombosis was significantly higher (p=0.022). All patients with COVID-19 had pulmonary involvement. No statistically significant difference was observed between the two groups in the comparison of post-stroke disorders. There was no statistically significant difference between the two groups in terms of BMRS, FIM and FAS values before and after treatment (p&gt;0.05). The change in BMRS, FIM and FAS values within both groups was found statistically significant. According to the results of this study, COVID-19-related stroke is seen at younger ages and deep vein thrombosis is more common. Significant improvements are observed in motor and functional status after rehabilitation. Rehabilitation should be given importance in patients with COVID-19-related stroke, and care should be taken in terms of deep vein thrombosis during rehabilitation.

Association of ischemic stroke onset time with presenting severity, acute progression, and long-term outcome: A cohort study.

Preclinical data suggest circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with inactive phase (daytime) than active phase (nighttime) stroke onset. We aimed to examine the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke. In a Korean nationwide multicenter observational cohort study from May 2011 to July 2020, we assessed circadian effects on initial stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at admission), END, and favorable functional outcome (3-month modified Rankin Scale [mRS] score 0 to 2 versus 3 to 6). We included 17,461 consecutive patients with witnessed ischemic stroke within 6 hours of onset. Stroke onset time was divided into 2 groups (day-onset [06:00 to 18:00] versus night-onset [18:00 to 06:00]) and into 6 groups by 4-hour intervals. We used mixed-effects ordered or logistic regression models while accounting for clustering by hospitals. Mean age was 66.9 (SD 13.4) years, and 6,900 (39.5%) were women. END occurred in 2,219 (12.7%) patients. After adjusting for covariates including age, sex, previous stroke, prestroke mRS score, admission NIHSS score, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, prestroke antiplatelet use, prestroke statin use, revascularization, season of stroke onset, and time from onset to hospital arrival, night-onset stroke was more prone to END (adjusted incidence 14.4% versus 12.8%, p = 0.006) and had a lower likelihood of favorable outcome (adjusted odds ratio, 0.88 [95% CI, 0.79 to 0.98]; p = 0.03) compared with day-onset stroke. When stroke onset times were grouped by 4-hour intervals, a monotonic gradient in presenting NIHSS score was noted, rising from a nadir in 06:00 to 10:00 to a peak in 02:00 to 06:00. The 18:00 to 22:00 and 22:00 to 02:00 onset stroke patients were more likely to experience END than the 06:00 to 10:00 onset stroke patients. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, falling from a peak at 06:00 to 10:00 to a nadir at 22:00 to 02:00. Study limitations include the lack of information on sleep disorders and patient work/activity schedules. Night-onset strokes, compared with day-onset strokes, are associated with higher presenting neurologic severity, more frequent END, and worse 3-month functional outcome. These findings suggest that circadian time of onset is an important additional variable for inclusion in epidemiologic natural history studies and in treatment trials of neuroprotective and reperfusion agents for acute ischemic stroke.