Recurrent Cerebral Ischemic Events Research Articles

Safety and efficacy of Cardi-O-fix occluder for percutaneous closure of a patent foramen ovale

Background:Amplatzer occluder and Cardio-O-fix occluder are currently used in percutaneous closure of patent foramen ovale. However, there is still a lack of relevant reports comparison the differences between them. The aim of this study was to evaluate the short-term and mid-term safety and efficacy of the Cardi-O-fix occluder in preventing recurrent cerebrovascular events in patients with a patent foramen ovale (PFO).Methods:We enrolled 246 patients (105 men) with a PFO from May 30, 2013 to March 30, 2015 in this single-center prospective study. All patients were treated by PFO interventional closure, with the Cardi-O-fix PFO occluder being used in 180 patients and the Amplatzer PFO occluder being utilized in the remaining 66 patients. After the procedure, we verified the safety and efficacy of different devices using contrast transthoracic echocardiography.Results:Neither recurrent stroke nor death was encountered during the follow-up of 12 months. Transient ischemic attack (TIA) was noted in 2 patients (1.1%) in the Cardi-O-fix PFO occluder group, and 1 patient suffered from TIA (1.5%) in the Amplatzer PFO occluder group. Among them, only 1 patient exhibited a small right to left shunt (RLS). There was no statistical difference in recurrent cerebral ischemic events. Three cases of paroxysmal atrial fibrillation were observed in the Cardi-O-fix PFO occluder group. One reverted spontaneously to sinus rhythm and the other 2 cases had pharmacologic conversion to sinus rhythm. One case of paroxysmal atrial fibrillation occurred in the Amplatzer group, which underwent pharmacologic conversion to sinus rhythm. There was no significant difference between the 2 groups regarding incidence of arrhythmia. No occluder translocation, erosion, pericardial effusion, and puncture site bleeding were observed in the 2 groups within 12 months of follow-up. The complete closure rates of the Cardi-O-fix and Amplatzer PFO occluder devices at the 12 months after the procedure were 73.9% and 63.6%, respectively, and the effective closure rates were 90.6% and 86.4%, respectively. There was no statistically significant difference in the complete closure rate and effective occlusion rate (P > 0.05) between the devices.Conclusions:There was no significant difference in the short- and mid-term efficacy and safety between the Cardi-O-fix PFO occluder and Amplatzer PFO occluder. The efficacy and safety of the Cardi-O-fix occluder were comparable to those of the Amplatzer PFO occluder.

Abstract TMP119: Early Cerebral Ischemic Events in Symptomatic Carotid Stenosis are Related to Plaque Inflammation

Background and aims: Symptomatic carotid stenosis is associated with an increased risk of early stroke recurrence. Severity of the stenosis, current basis of revascularization, explains only the cerebral ischemic mechanism of regional hypoperfusion. Plaque inflammation, the initiating event for plaque rupture and thromboembolism (artery-to-artery embolism), is not evaluated routinely. Using 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography (CT) and high resolution magnetic resonance imaging (HR-MRI), we investigated the role of plaque imaging and stroke recurrence in our cohort of stroke patients with recently symptomatic carotid stenosis. Methods: This ongoing prospective study included consecutive patients within 30-days of recent stroke and ipsilateral carotid stenosis (≥50%). FDG uptake was quantified as mean standardized uptake values (SUV, g/ml). The ratio of T1 hyperintensity of carotid plaque to the ipsilateral sternocleidomastoid muscle (SCM) was recorded on T1-weighted fat suppressed images. Patients were followed prospectively for stroke recurrence within 90-days. Embolic potential of carotid plaque is estimated by presence of spontaneous microembolic signals (MES) on extended transcranial Doppler monitoring of ipsilateral middle cerebral artery. Results: Of the 33 patients included in the study, 6 (18%) suffered from recurrent cerebral ischemic event in the same vascular territory within 90-days. Compared to patients without subsequent cerebral ischemic events, patients with recurrent cerebral ischemia showed higher mean T1 carotid-SCM ratio (2.49 versus 1.53; p<0.0001) and higher mean SUV value in the carotid plaque (3.52g/ml versus 1.51g/ml; p<0.0001). Higher T1 carotid-SCM ratio on HR-MRI (OR 4.249, 95%CI 1.818-5.18; p<0.0001), higher mean SUV on FDG-PET (OR 3.050, 95%CI 5.586-28.571; p=0.005) and MES on TCD (OR 2.186, 95%CI 1.652-47.619;p=0.037) were independent predictors of recurrent cerebral ischemia. Conclusions: FDG-PET/CT and HR-MRI imaging of carotid stenosis helps in identification of patients at higher risk of subsequent cerebral ischemic events and may aid in better therapeutic decision-making.

Mid-term results of interventional closure of patent foramen ovale with the Occlutech Figulla® Flex II Occluder.

BackgroundPatients with a patent foramen ovale (PFO) who suffered from stroke, TIA or peripheral paradoxical embolism are at substantial risk for recurrent neurologic events and in need for secondary prevention. Interventional closure of PFO has been performed for over 20 years. Numerous devices have been developed and used for treatment. We investigated PFO closure with the third generation Occlutech Figulla® Flex II Occluder device.MethodsBetween 2012 and 2015 57 patients (mean age 47.3 ± 1.5 years) who had suffered from a thromboembolic event of unknown cause underwent transcatheter PFO closure with the Occlutech Figulla® Flex II Occluder at our department. 68.4 % of all patients had suffered from cryptogenic stroke, while TIA had occurred in 28.1 %. Almost all patients were diagnosed with an atrial septum aneurysm (90.9 %) and a severe right-to-left shunt grade 3: >20 microbubbles (92.0 %). Follow-up was done 6 months post intervention by clinical examination and transesophageal contrast echocardiography.ResultsNo major periprocedural or in-hospital complication occurred. Closure was sufficient with no residual right-to-left shunt in 94.4 % of all patients at 6 months post implantation and only minimal residual shunt in three cases. There were no thrombotic formations associated to the occluder device. Atrial fibrillation occurred in one patient and a recurrent cerebral ischemic event was seen in one patient, who suffered from another TIA.ConclusionsThe Occlutech Figulla® Flex II Occluder device and its delivery system is safe and provides sufficient closure of PFO in patients who suffered from cryptogenic stroke, TIA or paradoxical peripheral embolism.

Long‐Term Outcomes and Complications of Intracardiac Echocardiography‐Assisted Patent Foramen Ovale Closure in 1,000 Consecutive Patients

Long-term fate of patients submitted to patent foramen ovale (PFO) closure is still unclear. The aim of the study was to evaluate the incidence of atrial fibrillation (AF), aortic or atrial free wall erosion, device thrombosis (DT), new onset or worsening of mitral valve regurgitation (MVR), and recurrent cerebral ischemic events in the long-term follow up after intracardiac echocardiography (ICE)-aided PFO closure in a large population. We reviewed the medical and instrumental data of 1,000 consecutive patients (mean age 47.3 ± 17.1 years, females) prospectively enrolled in 2 centres over a 13 years period (February 1999-February 2012) for R-to-L shunt ICE-aided catheter-based closure using different devices. Immediate success was 99.8%. Implanted devices were Amplatzer PFO Occluder in 463 patients (46.3%), Amplatzer ASD Cribriform Occluder in 420 patients (42.0%), Premere Occlusion System in 95 patients (9.5%), and Biostar Occluder in 22 patients (2.2%). On a mean follow-up of 12.3 ± 0.6 years (minimum 4- maximum 17 years), permanent AF occurred in 0.5%, DT was apparent in 0.5%, new onset or worsening of MVR was observed in 0.2%, whereas recurrent cerebral ischemic events were 0.8%. Occlusion rate was 93.8%. No aortic or atrial free wall erosion has been observed. ICE-aided closure of PFO using different devices, appeared very safe and effective on very long-term follow up with low incidence of erosion, DT, recurrent ischemic events, MVR new onset or worsening, and permanent AF.

The comparisons of phenotype and genotype between CADASIL and CADASIL-like patients and population-specific evaluation of CADASIL scale in China

BackgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary stroke disorder caused by mutations in the NOTCH3 gene. Although CADASIL scale is a widely used tool to screen clinically suspected CADASIL patients, the differential effects of this scale in various populations remain unknown.Methods92 CADASIL-like patients and 24 CADASIL patients were selected based on CADASIL scale and gene tests. The clinical, genetic and radiological characteristics were analyzed.ResultsBased on the CADASIL scale, we first screened 116 suspected CADASIL patients, and detected 20 mutations in 24 CADASIL-patients (Specificity: 20.69 %). Surprisingly, we found that transient ischemic attack/stroke, migraine, cognitive decline, psychiatric disturbances and early onset age in CADASIL scale showed no differences between the CADASIL and the CADASIL-like patients (p > 0.05). Instead, recurrent cerebral ischemic events (58.33 %, p = 0.028) and positive family histories (p < 0.05) were more frequently observed in CADASIL patients. Moreover, compared with CADASIL-like patients (21.74 %), CADASIL patients demonstrated higher percentage of temporal pole involvements (58.33 %, p = 0.001), but not the external capsule involvements (66.67 %, p = 0.602), in MRI imaging. Further, we found that vascular risk factors could occur in both CADASIL patients and CADASIL-like patients, and therefore could not be used as the markers to differentiate the two groups in our study (p > 0.05). By performing DSA analysis, we for the first time identified dysplasia of cerebral blood vessels in CADASIL patients, which were detected more frequently in CADASIL patients (41.67 %) in comparison with CADASIL-like patients (8.69 %, p <0.01).ConclusionOur data suggested that the efficacy of CADASIL scale to diagnose the disease varied with specific populations. Recurrent cerebral ischemic events, temporal pole involvements (but not the external capsule) in MRI imaging and dysplasia of cerebral blood vessels in DSA may be the new potential risk factors of the CADASIL scale suitable for Chinese patients. Gene testing by encephalopathy gene panel is expected to improve the accuracy of CADASIL differential diagnosis and increase the understanding of this disease in the future.

Abstract WP125: Plaque Inflammation Imaging in Carotid Stenosis and Recurrent Cerebral Ischemia

Background and aims: Symptomatic carotid stenosis is associated with an increased risk of early stroke recurrence. Currently, therapeutic decisions are largely based on the luminal narrowing, which mainly explain the cerebral ischemia related to regional hypoperfusion. Plaque inflammation, the initiating event for plaque rupture and thromboembolism (artery-to-artery embolism), is not evaluated routinely in patients with carotid stenosis. Using combined 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography (CT), we investigated the role of plaque inflammation and stroke recurrence in our cohort of stroke patients with recently symptomatic carotid stenosis. Methods: This ongoing prospective study aims to include consecutive patients within 30-days of recent stroke and ipsilateral carotid stenosis (≥50%). FDG uptake is quantified as mean standardized uptake values (SUV, g/ml). Patients are followed prospectively for stroke recurrence. Embolic potential of the carotid plaque is estimated by presence of spontaneous microembolic signals (MES) on continuous transcranial Doppler monitoring of the middle cerebral arteries (MCA) for 40 minutes. Results: Of the 22 patients included in the study, 5 suffered from recurrent cerebral ischemic event in the same vascular territory within 90 days. In patients with recurrent cerebral ischemia, the mean SUV value in the carotid plaque on the side of symptomatic carotid stenosis was higher (3.46g/ml) as compared to the patients without stroke recurrence (1.72g/ml; p=0.03). MES were noted in 3/5 cases with recurrent cerebral ischemia as compared to 2/17 cases (p=0.001) Conclusions: FDG-PET/CT aids in the imaging of plaque inflammation and identification of patients with higher risk of subsequent cerebral ischemic events. This ongoing study intends to develop a robust prediction model for risk stratification based on luminal stenosis and plaque characteristics for better therapeutic decision-making.

Severity assessment of intracranial large artery stenosis by pressure gradient measurements: A feasibility study.

Fractional flow reserve (FFR)-guided revascularization strategy is popular in coronary intervention. However, the feasibility of assessing stenotic severity in intracranial large arteries using pressure gradient measurements still remains unclear. Between March 2013 and May 2014, 12 consecutive patients with intracranial large artery stenosis (including intracranial internal carotid artery, middle cerebral M1 segment, intracranial vertebral artery, and basilar artery) were enrolled in this study. The trans-stenotic pressure gradient was measured before and/or after percutaneous transluminal angioplasty and stenting (PTAS), and was then compared with percent diameter stenosis. A Pd /Pa cut-off of ≤0.70 was used to guide stenting of hemodynamically significant stenoses. The device-related and procedure-related serious adverse events and recurrent cerebral ischemic events were recorded. The target vessel could be reached in all cases. No technical complications occurred due to the specific study protocol. Excellent pressure signals were obtained in all patients. For seven patients who performed PTAS, the mean pre-procedural pressure gradient decreased from 59.0 ± 17.2 to 13.3 ± 13.6 mm Hg after the procedure (P < 0.01). Only one patient who refused stenting experienced a TIA event in the ipsilateral MCA territory. No recurrent ischemic event was observed in other patients. Mean trans-stenotic pressure gradients can be safely and easily measured with a 0.014-inch fluid-filled guide wire in intracranial large arteries. © 2016 Wiley Periodicals, Inc.

Recurrent Ischemic Strokes and Headaches Originating from Lambl's Excrescences: A Case-Report

Determining recurrent stroke etiology and subsequent therapeutic approaches is an important, but not always straightforward task. Lambl’s Excrescences (LE) are cardiac valve strands that can be a source of recurrent cerebral ischemic events. We report the case of a 60 year old female that was seen in neurologic consultation for recurrent ischemic strokes. The patient developed migraine headache with complex auras at the age of 59. She reported three admissions for ischemic strokes in the past year. Stroke work-ups were unrevealing. The patient remained on daily Aspirin. Upon current admission, a brain MRI showed a combination of sub acute and chronic infarcts in diverse brain areas bilaterally. Further diagnostic evaluation revealed a relatively unremarkable CT head and neck angiogram. Transcranial Doppler (TCD) showed increased pulsatility index throughout the insonated vessels. Transesophageal echocardiogram (TEE) showed a trileaflet aortic valve with a 10 mm long thin fibrin strand prolapsing into the left ventricle outflow tract in diastole, meeting echocardiographic criteria for an LE. The patient refused anticoagulation and surgical intervention. She opted instead for a combination of two antiplatelet agents. Recurrent cerebral infarcts presenting concurrently with late-age onset migraine with aura should raise a clinical suspicion of cardiogenic valvular etiology. The use of TEE in evaluating patients with unexplained recurrent stroke is imperative so that LE is not missed. Anti-platelet agents, anti-coagulants, and cardiothoracic surgical intervention are proposed in the literature for the management of long-term complications associated with LE. Asymptomatic patients should be monitored, counseled, and made aware of LE complications, neurological symptoms, and alarm signals. Migraine headaches associated with LE should raise a red flag and prompt treatment with anti-platelet agents.

The role of advanced diagnostic technology in theselection of a patient with symptomatic but hemodynamically insignificant disease for carotid endarterectomy.

Current Level I evidence demonstrates no benefit for carotid endarterectomy in symptomatic patients with <50% carotid stenoses. However, unstable plaque morphology is increasingly recognized in the genesis of ischemic cerebral events. New advanced imaging technology, such as contrast-enhanced magnetic resonance angiography and ultrasound imaging, are emerging as important adjuncts in the evaluation of this patient population. We present a case where both modalities were beneficial in identifying plaque instability manifested by intraplaque hemorrhage and neovascularization in a patient with recurrent cerebral ischemic events and hemodynamically insignificant carotid disease.

PP-021 Idiopathic Left Ventricular Pseudo-aneurysm Presenting with Recurrent Cerebral Ischemic Events and Successful Treatment

PP-021 Idiopathic Left Ventricular Pseudo-aneurysm Presenting with Recurrent Cerebral Ischemic Events and Successful Treatment

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.

Patterns of Cerebral Ischemia in Children With Moyamoya

BackgroundMoyamoya disease is characterized by progressive cerebrovascular stenosis with recurrent cerebral ischemic events. Transient ischemic attacks are often associated with hyperventilation in children with moyamoya, suggesting hypoperfusion rather than thrombotic vaso-occlusion as a prominent mechanism. The patterns of ischemia and severity of steno-occlusive disease in such children may elucidate these mechanisms. MethodsChildren, 1 month to 18 years, with moyamoya, observed over 11 years were analyzed. A study neuroradiologist reviewed all presurgical neuroimaging. Ischemic injury was categorized into cortical, subcortical, and watershed infarction. Angiographic findings were staged using a standardized method. ResultsTwenty children, 15 girls, median age 6.4 years, were included. All children had magnetic resonance imaging and angiography, and in 16, conventional angiography was available. All 40 hemispheres, in 20 children, were evaluated. The initial clinical presentation included neurological deficits in 17, recurrent transient ischemic attacks in 7, headache in 8, seizures in 8, and alteration in consciousness in 4 children. Infarcts were bilateral in 13 (65%) children (ischemia alone in 14, ischemic stroke with hemorrhagic transformation in two, and primary hemorrhage in two). Infarcts were cortical and/or subcortical in 13 (65%), both deep and cortical watershed in 11 (55%), and cortical watershed alone in 5 (25%) children. The predominant vascular territory involved was the middle cerebral artery. The internal carotid arterial system was involved in all, with stage IV being the most frequent angiographic stage. ConclusionsIschemic injury in deep watershed zones is common in childhood moyamoya and may reflect non–vaso-occlusive ischemic mechanisms. Location and severity of vascular involvement may correlate with various patterns of ischemic infarction in moyamoya disease and requires further study.

William M. Feinberg award for excellence in clinical stroke: hemodynamics and stroke risk in carotid artery occlusion.

Five percent to 15% of patients with carotid territory transient ischemic attacks or cerebral infarctions have complete occlusion of the internal carotid artery.1,2 Their risk of recurrent stroke during the next 2 years while on medical therapy is 5% to 9% per year for all stroke and 2% to 8% per year for ipsilateral ischemic stroke.3–6 Debate on the best means to prevent recurrence has centered on whether embolic or hemodynamic mechanisms are most important. In the late 1970s and early 1980s, embolism of atherothrombotic material from the persisting proximal stump of the occluded internal carotid artery through external carotid artery collaterals was put forward as the most common cause for recurrent cerebral ischemic events.7,8 At this same time, extracranial–intracranial (EC-IC) bypass was increasingly used to prevent recurrent stroke by improving the hemodynamic status of the cerebral circulation distal to the occluded vessel.9,10 From 1977 to 1985, an international, multicenter, randomized trial was conducted to determine the efficacy of EC-IC bypass for the prevention of subsequent stroke. Among 808 randomized patients with symptomatic carotid occlusion, no benefit of surgery was demonstrated.11 Some concluded that the reason for the negative results was that the majority of strokes were because of emboli, whereas others criticized the trial for failing to identify patients with hemodynamic cerebral ischemia because of poor collateral circulation for whom surgical revascularization would be of benefit.12,13 However, the pattern of arteriographic collaterals failed to identify a subgroup who benefitted from surgery.14 At the time of the EC-IC Bypass Study, there was no reliable method for assessing the hemodynamic effects of carotid artery occlusion on cerebral circulation. Although direct measurements of arterial-jugular venous oxygen differences had demonstrated that reductions in whole-brain cerebral blood …

Abstract T MP29: Impaired Vasodilatory Reserve on Acetazolamide-Challenged 99tc-hmpao-Spect is a Strong Predictor of Stroke Recurrence in Patients With Severe Steno-Occlusive Disease of Intracranial Carotid or Middle Cerebral Artery

Background: Intracranial stenosis carries an increased risk for cerebrovascular ischemia. In severe stenosis, cerebral autoregulation may be impaired due to inadequate cerebral vasodilatory reserve (CVR) &amp; intracranial steal phenomenon (reversed-Robin Hood syndrome-RRHS). Identification of patients with inadequate CVR and RRHS may help in identifying high-risk patients. Methods: In this prospective study, we included patients with symptomatic and severe stenosis of intracranial carotid (ICA) &amp; middle cerebral artery (MCA). CVR was evaluated with transcranial Doppler (TCD) and breath-holding index (BHI) &lt;0.69 determined inadequate CVR. RRHS was detected as transient velocity reduction in affected artery when flow increased in the reference artery. Patients with RRHS were further evaluated with acetazolamide-challenged 99Tc-HMPAO-SPECT. Results: 126 patients (80 male, mean age 56yrs; range 23-78yrs) fulfilled our TCD criteria for inadequate CVR. HMPAO-SPECT showed impaired CVR in 84 (67%) patients. RRHS noted on TCD in 38 (45%) patients (median steal magnitude 14%; inter-quartile range, IQR 10) was confirmed by acetazolamide-challenged HMPAO-SPECT (median perfusion deficit 8%; IQR 13%) in 35 (92%) cases (sensitivity 82%, specificity 96% with positive predictive value 96%). A strong relationship between RRHS on TCD and SPECT was noted on ROC curve analysis (area under curve 0.93; 95% confidence interval 0.87-0.98;p&lt;0.00001). Linear relationship was observed between impaired vasodilatory reserve and stroke recurrence during follow up (mean 35months; range 8 to 49months)- 56% in patients with RRHS versus 20% in patients with moderately impaired CVR versus 4% in patients with mildly impaired CVR (chi-square 18.42; df=2; p&lt;0.001 for trend). RRHS on HMPAO-SPECT was an independent predictor of recurrent cerebral ischemic events (RR 1.9, 95%CI 1.2-4.2; p=0.03). Conclusions: Among patients with severe intracranial stenosis, intracranial steal phenomenon is associated with high risk of cerebral ischemic events. Acetazolamide-challenged HMPAO-SPECT is reliable in the quantification of vasodilatory reserve for selecting a target group of patients for possible revascularization.

The key areas of medical therapy for ischemic stroke

The paper considers the main therapeutic and preventive areas of management of patients with stroke, which are relied on evidence-based medicine data. To treat stroke patients is a multistep and multidisciplinary problem that starts with the emergence of the first neurological symptoms and extends over the entire life. Each period, including factors, such as the pattern of prehospital first medical aid; the rate of patient delivery to hospital; further actions of medical staff; measures for the prevention of recurrent cerebral ischemic events, cardiac complications, and cognitive disorders, is of importance in itself and serves a common aim. All efforts must aim eventually to reduce death rates in acute stroke, patient functional dependence, and recurrent brain damage rates, to prevent and timely treat cognitive impairments, to strictly adhere to the principles of secondary treatment of cardiovascular events in order to increase life expectancy and quality.

C-reactive protein after stroke in arterial hypertension.

To evaluate the relationship between plasma high-sensitivity C-reactive protein level and the risk of recurrent coronary and cerebral ischemic events after ischemic stroke in patients with arterial hypertension. 102 patients with mild-to-moderate arterial hypertension (67 male, aged 56-68 years) were enrolled in the study. Serum high-sensitivity C-reactive protein was determined on study entry only. Clinical interviews were performed every 3 months during 1 year after blood sampling. Clinical events included confirmed ischemic stroke or transient ischemic attack, coronary ischemic events, sudden death, diabetes mellitus, and all cardiovascular events including chronic heart failure and hospitalization. Patients in the highest quartile of high-sensitivity C-reactive protein levels had a significantly higher adjusted odds ratio for clinical events compared to those in the first quartile (odds ratio = 7.46, 95% confidence interval: 1.55-19.6, p = 0.001). A receiver operating characteristic curve detected a plasma high-sensitivity C-reactive protein cutoff level of 5.58 mg·L(-1) (76.7% sensitivity, 80.3% specificity). A Cox regression model identified high-sensitivity C-reactive protein >5.58 mg·L(-1) as an independent predictor of further cardiovascular events (hazard ratio = 7.14, 95% confidence interval: 1.15-12.6, p = 0.009). We suggest that high-sensitivity C-reactive protein levels >5.58 mg·L(-1) strongly predict increased risk of cumulative cardiovascular events after ischemic stroke in hypertensive patients.

Vascular endothelial growth factor-1 as a predictor of unfavorable cardiovascular events in arterial hypertension patients after ischemic stroke

Cardiologia CROATICA Objective: Circulating vascular endothelial growth factor-1 (VEGF-1) is considered as neuroprotective factor with angiopoetic capacity. However, interrelationship between VEGF-1 and frequency of recurrent cardiovascular outcomes in hypertensive patients after stroke in long-term follow-up is still uncertain. Aim: To evaluate the relationship between VEGF-1 and risk of recurrent coronary and cerebral ischemic events in arterial hypertension patients after the stroke. Methods: 102 mild-in-moderate arterial hypertension patients were enrolled to the in study 3 weeks after ischemic stroke and then they were being studied prospectively for 12 months period regarding survival rate and unfavorable clinical outcomes. Circulating VEGF-1 level was determined in the study entry only. Clinical interviews were performed every 3 months during 1 year after blood sampling. Results: Analysis of obtained outcomes showed that medians of circulating VEGF-1 levels in hypertensive patients after stroke, which demonstrated one, two, three or more cases of recurrent cardiovascular events were 373.80 pg/ml (95%CI=342.90-479.70 pg/mL), 539.96 pg/ml (95%CI= 444.28-865.56 g/mL), and 724.66 pg/mL (95% CI= 558.72890.66 pg/mL) respectively, and they were significantly higher than that of the persons for whom new clinically relevant cardiovascular outcomes were not documented (Me= 289.28 pg/mL, 95% CI=279.71-345.88 pg/mL) (P=0.001 for all cases). The cutoff point of VEGF-1 with the most optimal predictive value for recurrent cardiovascular events was equal to 403.57 pg/mL (area under the curve= 0.76, 95%CI=0.602-0.917, P=0.001, sensitivity=78.6% and specificity=70.0% respectively). In this case, when circulating VEGF-1 level was more than 403.57 pg/ml, the number of reported cardiovascular events during one year follow-up was significantly higher in comparison to lower levels of one (OR=4.11, 95%CI=2.66-7.28, P=0.001). Kaplan-Meier curves began to divide about 10 weeks after the study entry and achieved a significant difference in 14 weeks. After that a difference in events occurrence between the two patient cohorts with circulating VEGF-1 level less and more 403.57 pg/mL continued to deepen. Conclusion: We found that circulating vascular endothelial growth factor-1 level was an independent predictor of 1 year cumulative cardiovascular events in hypertensive patients after ischemic stroke.

Васкулярный эндотелиальный фактор роста-1 как предиктор неблагоприятных кардиоваскулярных событий у пациентов с гипертонической болезнью III стадии. Результаты одногодичного наблюдения. Часть I

Целью исследования явилось изучение взаимосвязи между циркулирующим уровнем васкулярного эндотелиального фактора роста-1 (VEGF-1) и частотой наступления повторных коронарных и церебральных ишемических событий у больных артериальной гипертензией (АГ) III стадии.Материал и методы. В исследование были включены 102 пациента с гипертонической болезнью III ст. легкой и умеренной степени тяжести через 3 недели после перенесенного мозгового ишемического инсульта. Период наблюдения составил 12 месяцев с 3-месячными интервалами. Циркулирующий уровень VEGF-1 оценивался однократно в начале исследования. Клинические интервью проводились каждые 3 месяца в течение 1 года после получения образцов крови. В качестве клинических точек учитывались все кардиоваскулярные исходы.Результаты. Анализ полученных данных показал, что медианы циркулирующих уровней VEGF-1 у больных с АГ III стадии, продемонстрировавших 1, 2, 3 случая и более повторных сердечно-сосудистых событий, составляют 373,80 пг/мл (95% ДИ 342,90–479,70 пг/мл), 539,96 пг/мл (95% ДИ 444,28–865,56 пг/мл) и 724,66 пг/мл (95% ДИ 558,72–890,66 пг/мл) соответственно, что достоверно превышает таковой у лиц, для которых новые клинически значимые кардиоваскулярные исходы документированы не были (Ме 289,28 пг/мл; 95% ДИ 279,71–345,88 пг/мл) (P = 0,001 для всех случаев). Наиболее оптимальной в отношении предсказующей ценности для будущих кардиоваскулярных событий является точка разделения VEGF-1, равная 403,57 пг/мл (площадь под кривой = 0,76; 95% ДИ 0,602–0,917; P = 0,001) при чувствительности и специфичности 78,6 и 70,0 % соответственно. При этом у обследованных лиц при уровне циркулирующего VEGF-1 более 403,57 пг/мл количество зарегистрированных кардиоваскулярных событий в течение одного года наблюдения было достоверно выше по сравнению с лицами с более низким уровнем VEGF-1 (OШ 4,11; 95% ДИ 2,66–7,28; P = 0,001).Вывод. Циркулирующий уровень васкулярного эндотелиального фактора роста-1 является независимым предиктором возникновения кумулятивных кардиоваскулярных исходов у больных с гипертонической болезнью III стадии на протяжении 1 года после мозгового ишемического инсульта.

Carotid plaque hemorrhage on magnetic resonance imaging strongly predicts recurrent ischemia and stroke

ObjectiveThere is a recognized need to improve selection of patients with carotid artery stenosis for carotid endarterectomy (CEA). We assessed the value of magnetic resonance imaging (MRI)-defined carotid plaque hemorrhage (MRIPH) to predict recurrent ipsilateral cerebral ischemic events, and stroke in symptomatic carotid stenosis.MethodsOne hundred seventy-nine symptomatic patients with ≥50% stenosis were prospectively recruited, underwent carotid MRI, and were clinically followed up until CEA, death, or ischemic event. MRIPH was diagnosed if the plaque signal intensity was >150% that of the adjacent muscle. Event-free survival analysis was done using Kaplan–Meier plots and Cox regression models controlling for known vascular risk factors. We also undertook a meta-analysis of reported data on MRIPH and recurrent events.ResultsOne hundred fourteen patients (63.7%) showed MRIPH, suffering 92% (57 of 62) of all recurrent ipsilateral events and all but 1 (25 of 26) future strokes. Patients without MRIPH had an estimated annual absolute stroke risk of only 0.6%. Cox multivariate regression analysis proved MRIPH as a strong predictor of recurrent ischemic events (hazard ratio [HR] = 12.0, 95% confidence interval [CI] = 4.8–30.1, p < 0.001) and stroke alone (HR = 35.0, 95% CI = 4.7–261.6, p = 0.001). Meta-analysis of published data confirmed this association between MRIPH and recurrent cerebral ischemic events in symptomatic carotid artery stenosis (odds ratio = 12.2, 95% CI = 5.5–27.1, p < 0.00001).InterpretationMRIPH independently and strongly predicts recurrent ipsilateral ischemic events, and stroke alone, in symptomatic ≥50% carotid artery stenosis. The very low stroke risk in patients without MRIPH puts into question current risk–benefit assessment for CEA in this subgroup. ANN NEUROL 2013;73:774–784

Lower Prevalence of Carotid Plaque Hemorrhage in Women, and Its Mediator Effect on Sex Differences in Recurrent Cerebrovascular Events

Background and PurposeWomen are at lower risk of stroke, and appear to benefit less from carotid endarterectomy (CEA) than men. We hypothesised that this is due to more benign carotid disease in women mediating a lower risk of recurrent cerebrovascular events. To test this, we investigated sex differences in the prevalence of MRI detectable plaque hemorrhage (MRI PH) as an index of plaque instability, and secondly whether MRI PH mediates sex differences in the rate of cerebrovascular recurrence.MethodsPrevalence of PH between sexes was analysed in a single centre pooled cohort of 176 patients with recently symptomatic, significant carotid stenosis (106 severe [≥70%], 70 moderate [50–69%]) who underwent prospective carotid MRI scanning for identification of MRI PH. Further, a meta-analysis of published evidence was undertaken. Recurrent events were noted during clinical follow up for survival analysis.ResultsWomen with symptomatic carotid stenosis (50%≥) were less likely to have plaque hemorrhage (PH) than men (46% vs. 70%) with an adjusted OR of 0.23 [95% CI 0.10–0.50, P<0.0001] controlling for other known vascular risk factors. This negative association was only significant for the severe stenosis subgroup (adjusted OR 0.18, 95% CI 0.067–0.50) not the moderate degree stenosis. Female sex in this subgroup also predicted a longer time to recurrent cerebral ischemic events (HR 0.38 95% CI 0.15–0.98, P = 0.045). Further addition of MRI PH or smoking abolished the sex effects with only MRI PH exerting a direct effect.Meta-analysis confirmed a protective effect of female sex on development of PH: unadjusted OR for presence of PH = 0.54 (95% CI 0.45–0.67, p<0.00001).ConclusionsMRI PH is significantly less prevalent in women. Women with MRI PH and severe stenosis have a similar risk as men for recurrent cerebrovascular events. MRI PH thus allows overcoming the sex bias in selection for CEA.