Recurrent Ischemic Stroke In Patients Research Articles

High serum levels of malondialdehyde and antioxidant enzymes are associated with post-stroke anxiety.

Post-stroke anxiety (PSA) is a common neuropsychiatric affective disorder occurring after stroke. The purpose of this study was to investigate the association between anxiety and the serum levels of oxidative stress markers at admission. First-ever or recurrent ischemic stroke patients were consecutively recruited into the study and followed up 1month. Patients were divided into PSA and non-PSA group according DSM-IV criteria for anxiety due to stroke. Overall, 49 patients (24.1%) were diagnosed anxiety. Serum GPX (glutathione peroxidase), CAT (catalase), SOD (superoxide dismutase), and MDA (malondialdehyde) were significantly higher in patients with anxiety than patients without anxiety. The HAM-A scores had a significant positive association with MDA levels. In multivariate logistic regression analysis, serum antioxidant enzymes and MDA were independent predictors of PSA. An increased risk of PSA was associated with serum MDA levels ≥ 3.0nmol/ml (adjusted OR 8.68, 95% CI 3.02-24.95; P < 0.001) after adjusting for relevant confounders such as social support and treatments at admission. Elevated serum levels of lipid oxidation products and antioxidant enzymes at admission were associated with anxiety 1month after stroke, suggesting that these alterations might participate in the pathophysiology of anxiety symptoms in stroke patients.

Timing of oral anticoagulant therapy in acute ischemic stroke with atrial fibrillation: study protocol for a registry-based randomised controlled trial

BackgroundOral anticoagulation therapy is recommended for the prevention of recurrent ischemic stroke in patients with atrial fibrillation (AF). Current guidelines do not provide evidence-based recommendations on optimal time-point to start anticoagulation therapy after an acute ischemic stroke. Non-vitamin K antagonist oral anticoagulants (NOACs) may offer advantages compared to warfarin because of faster and more predictable onset of action and potentially a lower risk of intracerebral haemorrhage also in the acute phase after an ischemic stroke. The TIMING study aims to establish the efficacy and safety of early vs delayed initiation of NOACs in patients with acute ischemic stroke and AF.Methods/DesignThe TIMING study is a national, investigator-led, registry-based, multicentre, open-label, randomised controlled study. The Swedish Stroke Register is used for enrolment, randomisation and follow-up of 3000 patients, who are randomised (1:1) within 72 h from ischemic stroke onset to either early (≤ 4 days) or delayed (≥ 5–10 days) start of NOAC therapy. The primary outcome is the composite of recurrent ischemic stroke, symptomatic intracerebral haemorrhage, or all-cause mortality within 90 days after randomisation. Secondary outcomes include: individual components of the primary outcome at 90 and 365 days; major haemorrhagic events; functional outcome by the modified Rankin Scale at 90 days; and health economics. In an optional biomarker sub-study, blood samples will be collected after randomisation from approximately half of the patients for central analysis of cardiovascular biomarkers after study completion. The study is funded by the Swedish Medical Research Council. Enrolment of patients started in April 2017.ConclusionThe TIMING study addresses the ongoing clinical dilemma of when to start NOAC after an acute ischemic stroke in patients with AF. By the inclusion of a randomisation module within the Swedish Stroke Register, the advantages of a prospective randomised study design are combined with the strengths of a national clinical quality register in allowing simplified enrolment and follow-up of study patients. In addition, the register adds the possibility of directly assessing the external validity of the study findings.Trial registrationClinicalTrials.gov, NCT02961348. Registered on 8 November 2016.

Transesophageal echocardiographic findings associated with recurrent ischemic stroke in patients with embolic stroke of undetermined source (ESUS)

Transesophageal echocardiographic findings associated with recurrent ischemic stroke in patients with embolic stroke of undetermined source (ESUS)

Hyperglycemia in acute ischemic stroke: Is it time to re-evaluate our understanding?

Among 700,000 new and recurrent ischemic stroke patients per year, forty percent are hyperglycemic on admission. In-vitro, hyperglycemia is toxic to neurons. Acute ischemic stroke patients who are hyperglycemic on admission experience higher morbidity and mortality. Results of multiple trials have provided no evidence supporting benefit in achieving normoglycemia. On the contrary, there is some evidence that tight glycemic control in acute brain injury is associated with poor outcome. Current consensus derived guidelines from the American Heart Association/American Stroke Association recommend an upper limit of blood glucose of 140–180mg/dl, as there is no evidence to support strict control. The lack of improved outcomes with normoglycemia in this population dictates reconsideration of assumptions regarding the underlying pathophysiology of hyperglycemia. Review of the current data suggests there are two distinct pathophysiologic entities of hyperglycemia in acute ischemic stroke patients: diabetic and non-diabetic. We propose that the lack of positive results from well-designed intention-to-treat trials in hyperglycemic acute ischemic stroke patients could be attributed to treating these distinct groups as one.

Abstract TMP100: Outpatient Statin Adherence is Associated with Reduced Recurrent Stroke Risk in Patients with or without Atrial Fibrillation

Outpatient statin use is known to reduce the risk of recurrent ischemic stroke of atherothrombotic etiology, but it is not known whether statins have similar effects in ischemic stroke associated with atrial fibrillation (AF). We examined the relationship between outpatient statin adherence and the risk of recurrent ischemic stroke in patients with or without AF in a large integrated healthcare delivery system. Among 6,283 patients with ischemic stroke discharged on a statin over a 5 year period, 1,486 (23.7%) had a diagnosis of AF at discharge. Statin adherence rates, measured as percentage of days covered (PDC), averaged 85% (88% for AF patients and 84% for non-AF patients). We observed up to three years after the initial stroke, with an average of two years follow up. In multivariable survival models, after controlling for age, gender, race/ethnicity, and key medical comorbidities, higher statin adherence was found to strongly predict a reduced risk of recurrent ischemic stroke (Figure). In the second year post-stroke, the hazard ratio (HR) associated with a 10% increase in PDC was 0.93 (95% C.I. 0.89-097). The relationship between statin adherence and reduced stroke rates was similar in AF patients (HR 0.94, 95% C.I. 0.84-0.98) and non-AF patients (HR 0.93, 95% C.I. 0.88-0.98). These findings support the use of outpatient statins in all ischemic stroke patients, irrespective of stroke etiology (atherothrombotic vs. atrial fibrillation).

Neutrophil-to-Lymphocyte Ratio Is a Prognostic Marker in Acute Ischemic Stroke

Neutrophil-to-lymphocyte ratio is an independent predictor of mortality in patients with acute ischemic stroke. However, it is uncertain whether neutrophil-to-lymphocyte ratio is related with functional outcome and recurrent ischemic stroke. In this study, we aimed to investigate the relationship of neutrophil-to-lymphocyte ratio with stroke severity, functional outcome, and recurrent ischemic stroke after acute ischemic stroke. A total of 280 patients with acute ischemic stroke were included in the study. Patients were divided into 3 groups according to the neutrophil-to-lymphocyte ratio value (<2, 2-3, >3). Demographic, clinical, and laboratory data were collected for all patients. We evaluated the association between neutrophil-to-lymphocyte ratio and (1) stroke severity on admission, (2) functional outcome at 3 months, and (3) recurrent ischemic stroke. Regression analyses were performed, adjusting for confounders. After adjustment for potential confounders, neutrophil-to-lymphocyte ratio was associated with an increased risk of stroke severity on admission (odds ratio [OR] 1.364, 95% confidence interval [CI] 1.101-1.690, P = .005) and primary unfavorable outcome (OR 1.455, 95% CI 1.083-1.956, P = .013). After a median of 1.13 years (interquartile range.91-1.42) of follow-up, neutrophil-to-lymphocyte ratio was associated with recurrent ischemic stroke after adjustment (hazard ratio 1.499, 95% CI 1.161-1.935, P = .002). Our study suggests that neutrophil-to-lymphocyte ratio is associated with stroke severity on admission, primary unfavorable functional outcome, and recurrent ischemic stroke in patients with acute ischemic stroke.

Commentary on ‘Risk of Recurrent Stroke in Patients with Symptomatic Mild (20–49% NASCET) Carotid Stenosis’

Commentary on ‘Risk of Recurrent Stroke in Patients with Symptomatic Mild (20–49% NASCET) Carotid Stenosis’

Risk of Recurrent Stroke in Patients with Symptomatic Mild (20–49% NASCET) Carotid Artery Stenosis

The objective of this study was to evaluate the risk of recurrent ischaemic stroke in patients with ultrasound assessed symptomatic mild carotid artery stenosis (20-49% NASCET) treated solely with modern medical treatment. This was a retrospective, observational register cohort study. Three groups of patients were recruited from a database of all carotid Doppler ultrasound examinations performed in the Gothenburg region between 2004 and 2009. Patients with symptomatic mild carotid artery stenosis (n=162) were compared with patients with asymptomatic carotid artery stenosis (n=301) of equal degree and a group of patients with surgically (CEA) treated symptomatic moderate or severe carotid artery stenosis (n=220). Kaplan-Meier estimates and Cox proportional hazard models were used to compare the primary outcome (ipsilateral ischaemic stroke) between groups. After a 3 year follow up, the cumulative incidence of recurrent ipsilateral stroke in patients with symptomatic mild carotid artery stenosis was 7.4%. Patients with symptomatic mild carotid artery stenosis had a substantially increased risk of recurrent ipsilateral stroke compared with asymptomatic patients with equal degree of stenosis (HR 5.5. 95% CI 1.8-17.1; p=.003) as also compared with patients with CEA treated symptomatic moderate or severe stenosis (HR 7.8. 95% CI 1.62-37.8; p=.011). The present study on patients with symptomatic mild carotid artery stenosis, as determined by Doppler ultrasound, shows that there is still a substantial risk of recurrent stroke in this group.

H-Type Hypertension and C Reactive Protein in Recurrence of Ischemic Stroke

Hypertension with high homocysteine (HHcy) (H-type hypertension) and C reactive protein (CRP) can increase the incidence of ischemic stroke. However, it is not clear whether recurrent ischemic stroke (RIS) is related to H-type hypertension and CRP. The present study investigated the correlation of H-type hypertension and CRP level with RIS. Totally, 987 consecutive patients with acute ischemic stroke were recruited in a teaching hospital in Henan province, China during March 2014 to March 2015. The demographic and clinical characteristics and blood biochemical parameters of patients were analyzed. Elevated levels of CRP and homocysteine (Hcy) were defined as >8.2 mg/L and 10 μmol/L, respectively. Among the 987 patients, 234 were RIS. Thirty-eight percent of RIS patients had elevated CRP level and 91.5% of RIS patients had HHcy. In multivariate analysis, adjusted odds ratio (OR) of RIS in patients aged ≥60 years was 1.576 (95% CI: 1.125–2.207), in male patients 1.935 (95% CI: 1.385–2.704), in patients with diabetes 1.463 (95% CI: 1.037–2.064), CRP levels 1.013 (95% CI: 1.006–1.019), simple hypertension 3.370 (95% CI: 1.15–10.183), and H-type hypertension 2.990 (95% CI: 1.176–7.600). RIS was associated with older age, male, diabetes, H-type hypertension and CRP. Controlling H-type hypertension and CRP level may reduce the risk of RIS.

Timing of anticoagulation therapy in patients with acute ischaemic stroke and atrial fibrillation.

In patients with acute stroke and atrial fibrillation (AF), the risk of early recurrence has been reported to range between 0.1 % and 1.3 % per day. Anticoagulants are the most effective therapy for the prevention of recurrent ischaemic stroke in these patients, but randomised clinical trials have failed to produce any evidence supporting the administration of heparin within 48 hours from stroke onset as it has been associated with a non-significant reduction in the recurrence of ischaemic stroke, no substantial reduction in death and disability, and an increase in intracranial bleeding. As early haemorrhagic transformation is a major concern in the acute phase of stroke patients with AF, determining the optimal time to start anticoagulant therapy is essential. This review which focuses on the epidemiology of recurrent ischaemic stroke and haemorrhagic transformation in patients with acute ischaemic stroke and AF, proposes a model for decision making on optimal timing for initiating anticoagulation, based on currently available evidence.

Impact of 5A/6A polymorphism of matrix metalloproteinase-3 on recurrent atherosclerotic ischemic stroke in Chinese

Little is known about the impact of the 5A/6A polymorphism of matrix metalloproteinase-3 (MMP-3) on recurrence of atherosclerotic ischemic stroke in Chinese. The aim of this study was to investigate the association of MMP-3 serum level and 5A/6A genetic polymorphism with the recurrence of atherosclerotic ischemic stroke in the Chinese Han population. We analyzed 106 large artery atherosclerosis (LAA) recurrent ischemic stroke patients and 545 LAA first onset ischemic stroke patients from January 2009 to June 2014. Serum MMP-3 concentrations were measured with an enzyme-linked immunosorbent assay. The genotypes of MMP-3 promoter polymorphism (−1171 5A/6A) were determined using polymerase chain reaction-restriction fragment length polymorphism. The frequencies of MMP-3 5A/6A+5A/5A (32.08% vs. 21.47%, p = 0.02) genotype and 5A (16.98% vs. 11.01%, p = 0.01) allele in the recurrent group was significantly higher than those in the first onset group. After adjustment for vascular risk factors, multivariate logistic regression analysis suggested that the MMP-3 5A/6A+5A/5A genotype was an independent risk factor for LAA recurrent ischemic stroke (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.09–2.79, p = 0.021). No significant difference was observed for the MMP-3 serum concentrations between the recurrent group and the first onset group (22.23 ± 8.31 vs. 21.49 ± 7.89 ng/ul, t = 0.88, p = 0.38). The MMP-3 (−1171 5A/6A) polymorphism may contribute to LAA recurrent ischemic stroke susceptibility. Analysis of 5A/6A polymorphism in MMP-3 may identify patients at higher risk for LAA ischemic stroke recurrence, who may be selected for intensive preventive therapy.

Carotid Webs and Recurrent Ischemic Strokes in the Era of CT Angiography.

Carotid webs may cause recurrent ischemic stroke. We describe the prevalence, demographics, clinical presentation, imaging features, histopathology, and stroke risk associated with this under-recognized lesion. A carotid web was defined on CTA as a thin intraluminal filling defect along the posterior wall of the carotid bulb just beyond the carotid bifurcation on oblique sagittal section CTA that was seen as a septum on axial CTA. Using a prospective case series from April 2013 to April 2014, we describe the demographics, spectrum of imaging features on CTA, and histopathology of these carotid webs. From a retrospective analysis of patients at our center from May 2012 to April 2013 who had a baseline head and neck CTA followed by a brain MR imaging within 1-2 days of the CTA, we determine the period prevalence of carotid webs and the prevalence of ipsilateral stroke on imaging. In the prospective series, the mean age was 50 years (range, 41-55 years); 5/7 patients were women. Recurrent stroke was seen in 5/7 (71.4%) patients with the carotid web; time to recurrence ranged from 1 to 97 months. Histopathology suggested a high probability of fibromuscular dysplasia. In the retrospective series, carotid webs were seen in 7/576 patients for a hospital-based-period prevalence of 1.2% (95% CI, 0.4%-2.5%). Two of these 7 patients had acute stroke in the vascular territory of the carotid web. A carotid web may contribute to recurrent ischemic stroke in patients with no other determined stroke mechanism. Intimal variant fibromuscular dysplasia is the pathologic diagnosis in most cases. The prevalence of carotid web is low, while the optimal management strategy remains unknown.

Abstract 208: Vascular Risk Factors But Not Transesophageal Echocardiography (TEE) Features Are Associated With Stroke Recurrence in Patients With Cryptogenic Stroke (CS) and Patent Foramen Ovale (PFO)

Background and purpose: Recurrent ischemic stroke in patients with CS and PFO has been proposed as a marker of increased risk for paradoxical embolism. It is unclear, whether the excess risk is driven by specific features of the PFO (right-to-left shunt (RLS) size, RLS at rest, associated atrial septum aneurysm (ASA)) or the presence of vascular risk factors (vRF). We compare the prevalence of vRF, TEE features, and baseline medications in PFO patients with first-ever versus multiple CS. Methods: From September 2008 to March 2013, the International PFO Consortium enrolled 993 patients with ischemic stroke or transient ischemic attack (TIA) and newly diagnosed PFO. In this analysis of baseline data, we included 386 patients with first-ever CS and no radiological evidence of prior cerebral ischemia (first-ever CS group, mean age, 52y) as well as 71 patients with recurrent CS and multiple ischemic lesions on CT and/or MRI (multiple CS group, mean age, 59y). Patients with TIA as index event, those with first-ever CS but additional “silent” ischemic lesions on imaging as well as those with recurrent CS without radiological findings of prior cerebral ischemia were excluded. We used nonparametric tests for independent samples and the Bonferroni correction for multiple comparisons. Results: Age &gt; 55y (63% vs. 44%, P=0.001), hypertension (52% vs. 30%, P=0.001), hyperlipidemia (64% vs. 44%, P=0.003), and coronary artery disease (15% vs. 3%, P=0.001) were significantly more frequent in the multiple CS than in the first-ever CS group. The frequencies of male gender, current smoking, diabetes, migraine with or without aura, associated ASA, RLS size, and RLS at rest did not differ between groups. At baseline, patients with multiple CS were more likely to be on antiplatelets (50% vs. 18%), antihypertensive (51% vs. 22%) or lipid lowering drugs (44% vs. 10%, P=0.001 for each comparison) than patients with first-ever CS. The frequency of anticoagulant treatment did not differ between groups. Conclusions: In patients with CS, vRF but not specific PFO features were associated with recurrent cerebral ischemic events. The ongoing prospective part of the International PFO Consortium will likely shed light upon the role of vRF control for secondary stroke prevention in patients with PFO.

D-dimer for prediction of long-term outcome in cryptogenic stroke patients with patent foramen ovale.

Patent foramen ovale (PFO) is a potential cause of cryptogenic stroke, given the possibility of paradoxical embolism from venous to systemic circulation. D-dimer level is used to screen venous thrombosis. We investigated the risk of embolism and mortality according to the presence of PFO and D-dimer levels in cryptogenic stroke patients. A total of 570 first-ever cryptogenic stroke patients who underwent transesophageal echocardiography were included in this study. D-dimer was assessed using latex agglutination assay during admission. The association of long-term outcomes with the presence of PFO and D-dimer levels was investigated. PFO was detected in 241 patients (42.3 %). During a mean 34.0 ± 22.8 months of follow-up, all-cause death occurred in 58 (10.2 %) patients, ischaemic stroke in 33 (5.8 %), and pulmonary thromboembolism in 6 (1.1 %). Multivariate Cox regression analysis showed that a D-dimer level of > 1,000 ng/ml was an independent predictor for recurrent ischaemic stroke in patients with PFO (hazard ratio 5.341, 95 % confidence interval 1.648-17.309, p=0.005), but not in those without PFO. However, in patients without PFO, a D-dimer level of > 1,000 ng/ml was independently related with all-cause mortality. The risk of pulmonary thromboembolism tended to be high in patients with high D-dimer levels, regardless of PFO. Elevated D-dimer levels in cryptogenic stroke were predictive of the long-term outcome, which differed according to the presence of PFO. The coexistence of PFO and a high D-dimer level increased the risk of recurrent ischaemic stroke. The D-dimer test in cryptogenic stroke patients may be useful for predicting outcomes and deciding treatment strategy.

Functional gain following rehabilitation of recurrent ischemic stroke in the elderly: Experience of a post-acute care rehabilitation setting

The aim of the study was to evaluate whether rehabilitation of patients with recurrent ischemic strokes is associated with functional gain. We studied a total of 919 consecutive post-acute ischemic stroke elderly patients admitted for rehabilitation. 22% out of the patients had recurrent stroke on index day. Functional outcomes of first-ever stroke patients and recurrent ischemic stroke patients were assessed by the Functional Independence Measurement scale (FIM™) at admission and discharge. Data was analyzed by t-test, Chi-square test and by multiple linear regression analysis. There were 716 patients with first ever stroke and 203 patients with recurrent stroke. Total and motor FIM scores at admission and total, motor, gain and Montebello Rehabilitation Factor (RFG) FIM scores at discharge were similar in the two groups. A multiple linear regression analysis showed that age (beta=−0.13, p=0.001) length of stay (beta=0.21, p<0.001), Mini-Mental State Examination score (MMSE) (beta=0.1, p=0.01), and admission total FIM (beta=−0.12, p=0.01) emerged as the only independent predictors of higher gain FIM scores at discharge. The finding suggests that elderly patients with recurrent ischemic stroke admitted to rehabilitation ward, showed similar FIM gain scores at discharge, compared with first-ever stroke patients. It is concluded that recurrent stroke should not be considered as adversely affecting the short-term functional outcomes of patients in a post-acute rehabilitation setting.

Transcranial Doppler Ultrasonography CO2 Reactivity Does Not Predict Recurrent Ischaemic Stroke in Patients with Symptomatic Carotid Artery Occlusion

Background: Patients with transient ischaemic attacks (TIAs) or minor disabling ischaemic stroke associated with an internal carotid artery (ICA) occlusion have a high risk of recurrent stroke in case of compromised cerebral blood flow. Recent studies showed that increased oxygen extraction fraction measured by positron emission tomography (PET) is still an independent predictor of subsequent stroke under current medical treatment, but PET facilities are not widely available. Transcranial Doppler (TCD) ultrasonography CO₂ reactivity is a cheap and non-invasive alternative to measure haemodynamic compromise. The aim of our study was to investigate whether TCD CO₂ reactivity is an independent predictor of recurrent ischaemic stroke in a large cohort of patients with symptomatic ICA occlusion in a time where rigorous control of vascular risk factors has been widely implemented in clinical practice. Methods: Between July 1995 and December 2009, we included consecutive patients with TIAs or minor disabling ischaemic stroke (modified Rankin Scale ≤3) associated with ICA occlusion who were referred to the University Medical Centre Utrecht, The Netherlands. All patients were treated with antiplatelet therapy and received rigorous control of vascular risk factors, including statins, treatment for diabetes and hypertension and lifestyle advices. CO₂ reactivity was measured with TCD within 3 months after presentation. We determined the predictive value of TCD CO₂ reactivity for recurrent ischaemic stroke using Cox proportional hazard analysis. Results: We included 201 patients with a median follow-up time of 7.1 years. Mean CO₂ reactivity was 15% (±20 standard deviation). The annual rate for ipsilateral ischaemic stroke was 2.2% [95% confidence interval (CI) 1.4-3.2] and for any recurrent stroke 3.2% (95% CI 2.3-4.4). We did not find a significant relationship between CO₂ reactivity and the risk of ipsilateral [hazard ratio (HR) for every increase in percentage point 1.01, 95% CI 0.99-1.02] or any recurrent ischaemic stroke (HR 1.01, 95% CI 0.998-1.02). Multivariable analysis showed a significant relationship with history of stroke (HR 4.0, 95% CI 1.8-9.0) for ipsilateral recurrent stroke, and age (HR for increase per year 1.05, 95% CI 1.01-1.09) and a history of stroke (HR 3.4, 95% CI 1.7-6.6) for any recurrent stroke. Conclusions: In patients with TIAs or non-disabling stroke associated with occlusion of the carotid artery, the long-term annual risk of stroke is generally low with careful control of vascular risk factors. Impaired CO₂ reactivity measured within 3 months after presentation does not identify the subgroup of patients at high risk of recurrent ischaemic stroke.

Continued Statin Treatment After Acute Intracranial Hemorrhage

Statin therapy has clearly demonstrated a beneficial effect in reducing the risk of first ever and recurrent ischemic stroke in patients with coronary artery and cerebrovascular diseases. However, the overall benefit of statins in patients with previous stroke appears to be partially offset by an increased risk of intracranial hemorrhage (ICH). Post hoc analyses of 2 large randomized trials, Heart Protection Society and Stroke Prevention by Aggressive Reduction in Cholesterol Levels, suggest that patients with previous stroke may be at increased risk of hemorrhagic stroke independently of cholesterol levels.1 Like dynamite, statins help fighting fires (ischemic strokes), but with an added risk of potential collateral damages (ICH). Thus, avoidance of statin initiation or continuation after ICH has been recommended by several experts. In contrast, recent observational cohort studies and 1 meta-analysis found no evidence of increased risk of ICH in patients treated with statins after an ischemic stroke. Therefore, it is a matter of controversy whether continuation or initiation of statins in acute ICH patients with history of ischemic stroke is beneficial or harmful in terms of ICH growth, stroke (ischemic and hemorrhagic) recurrence and clinical outcome. Dr Goldstein, …

Association between estimated glomerular filtration rate, ankle-brachial index, and recurrent ischemic stroke in a Chinese population of ischemic stroke patients

Very few studies have examined combined association of estimated glomerular filtration rate (eGFR) and ankle-brachial index (ABI) on recurrent ischemic stroke in patients with ischemic stroke in Chinese populations. A Chinese population of 1219 ischemic stroke patients was followed up in this six-year prospective study. 1080 ischemic stroke patients with complete follow-up data were included in the statistical analysis. A total of 245 ischemic stroke patients (22.7 %) had recurrent ischemic stroke during follow-up. The Incidence of recurrent ischemic stroke was significantly increased with decreasing eGFR levels and that of patients with eGFR < 30 ml/min/1.73m2 was the highest. Hazard ratio (HR) of eGFR < 30 ml/min/1.73m2 to recurrent ischemic stroke was 2.633 (95 % CI: 1.653 - 4.194) compared with that of eGFR ≥ 60 ml/min/1.73m2 after adjusting for other potential confounders using Cox regression analysis. Incidence of recurrent ischemic stroke was significantly increased with simultaneously decreasing eGFR and ABI. The highest percentage (71.4 %) of patients with eGFR < 30 ml/min/1.73m2 and ABI ≤ 0.4 simultaneously had recurrent ischemic stroke during follow-up. HR of eGFR < 30 ml/min/1.73m2 and ABI ≤ 0.4 simultaneously with recurrent ischemic stroke was 9.415 (95 % CI: 3.479 - 25.483) compared with that of eGFR ≥ 60 ml/min/1.73m2 and ABI > 1.0 to ≤ 1.4 respectively Low ABI and low eGFR together had synergistic effects on increasing recurrent ischemic stroke of ischemic stroke patients during a long-term follow-up.

Closure of Patent Foramen Ovale versus Medical Therapy after Cryptogenic Stroke

BackgroundWhether closure of a patent foramen ovale is effective in the prevention of recurrent ischemic stroke in patients who have had a cryptogenic stroke is unknown. We conducted a trial to evaluate whether closure is superior to medical therapy alone in preventing recurrent ischemic stroke or early death in patients 18 to 60 years of age.MethodsIn this prospective, multicenter, randomized, event-driven trial, we randomly assigned patients, in a 1:1 ratio, to medical therapy alone or closure of the patent foramen ovale. The primary results of the trial were analyzed when the target of 25 primary end-point events had been observed and adjudicated.ResultsWe enrolled 980 patients (mean age, 45.9 years) at 69 sites. The medical-therapy group received one or more antiplatelet medications (74.8%) or warfarin (25.2%). Treatment exposure between the two groups was unequal (1375 patient-years in the closure group vs. 1184 patient-years in the medical-therapy group, P=0.009) owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat cohort, 9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke (hazard ratio with closure, 0.49; 95% confidence interval [CI], 0.22 to 1.11; P=0.08). The between-group difference in the rate of recurrent stroke was significant in the prespecified per-protocol cohort (6 events in the closure group vs. 14 events in the medical-therapy group; hazard ratio, 0.37; 95% CI, 0.14 to 0.96; P=0.03) and in the as-treated cohort (5 events vs. 16 events; hazard ratio, 0.27; 95% CI, 0.10 to 0.75; P=0.007). Serious adverse events occurred in 23.0% of the patients in the closure group and in 21.6% in the medical-therapy group (P=0.65). Procedure-related or device-related serious adverse events occurred in 21 of 499 patients in the closure group (4.2%), but the rate of atrial fibrillation or device thrombus was not increased.ConclusionsIn the primary intention-to-treat analysis, there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic ischemic stroke. However, closure was superior to medical therapy alone in the prespecified per-protocol and as-treated analyses, with a low rate of associated risks. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number, NCT00465270.)

Abstract 138: Gamma Delta TCR Lymphocytes and Immune Memory of Ischemic Stroke

Background: Inflammation plays an important role in ischemic stroke (IS) pathophysiology. Gamma/delta+ TCR (gdTCR), CD8+gdTCR, and CD4+ gdTCR lymphocytes are newly recognized contributors to innate immune systems responses. In experimental stroke models gdTCR lymphocytes have been found to contribute substantially to cerebral infarct growth and have the potential to contribute to immune memory after stroke. We aimed to determine whether changes in gdTCR cellular count and lymphocyte activity occur after human stroke, and if differences exist between first-ever and recurrent IS. Methods: First-ever IS patients (n=20), recurrent IS patients (n=29) and matched healthy control subjects (n=28) were studied. Blood was drawn within 72 hours of stroke onset and was stained with CD3 (PE-TR), gdTCR (PE), CD4 (FITC) and CD8 (PE-Cy5) monoclonal antibodies. The percentages of circulating gdTCR lymphocytes were evaluated by fluorescent-activated cell counter and analyzed using “FlowJo” software. The expression of selected inflammatory and stroke-related genes, based on previous reports, was measured in gdTCR lymphocytes isolated from 7 first-ever IS patients and 14 recurrent IS patients. Magnetic bead separation was used for cellular isolation and messenger ribonucleic acid expression was measured using digital polymerase chain reactions. Statistical analyses used Mann-Whitney U tests and chi-square tests. Results: The numbers of CD8+gdTCR cells were higher in all IS patients vs. control subjects (p=.04) and in recurrent IS patients vs. control subjects (p=.01). No difference was seen between first ever IS patients and control subjects (p=.4). Comparison of gdTCR cellular gene expression between recurrent IS patients and first-ever IS patients showed significantly higher expression of MMP9 (p=.02) and SLC2A3 (p=.04) in recurrent IS patients. TLR2 and IL23R were also borderline significantly higher in recurrent IS patients (0.05&lt;p&lt;0.1). No differences in gdTCR or CD4+ gdTCR counts were found between IS patients and controls. Conclusion: Alterations in gdTCR gene expression and in levels of the CD8+TCR subset in patients with recurrent stroke may indicate a potential role of the innate system in immune memory after ischemic stroke.