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Percutaneous transluminal angioplasty with stenting (PTAS) has become a treatment option for severe carotid stenosis. The goal of our study was to determine prospectively neurocognitive outcome 6 months after unilateral stent-protected carotid angioplasty. Twenty consecutive patients who underwent stent-protected angioplasty for symptomatic (n=9) or asymptomatic (n=11) high-grade carotid stenosis were investigated and compared to an age and disease matched control group. Patients were administered preprocedurally and 6 months postprocedurally a battery of neuropsychological tests. We used reliable change indices methodology in order to control for practice and statistical effects unrelated to intervention. We found no cognitive change in approximately 90% of patients and cognitive improvement in approximately 10% of patients for concentration and attention variables. We further found no cognitive change in 61% of patients, cognitive improvement in 11% of patients and cognitive deterioration in 28% of patients for psychomotor speed. No cognitive change in 94% of patients and cognitive deterioration in 6% of patients was found for sustained attention; no cognitive change in 80% of patients, cognitive improvement in 15% of patients and cognitive deterioration in 5% of patients was found for verbal fluency; no cognitive change in 100% of patients was found for interference (Stroop test): no cognitive change in 95% of patients, cognitive improvement in 5% of patients was found for interference (c.I. test), respectively. Our study showed that 6 months after PTAS cognitive functioning did not change in most patients significantly. For some patients, however, significant improvement or deterioration in single neurocognitive domains can be expected. The reasons for these changes are unclear but may depend on variable type; magnitude of microemboli production; right vs. left cerebral vasculature, respectively. [ABSTRACT FROM AUTHOR]

Genetic risk factors play an important role in the aetiology of vascular diseases. The insertion/deletion polymorphism (4G/5G) in the promotor region of the plasminogen activator inhibitor 1 (PAI-1) gene has been associated with an increased risk of myocardial infarction. We investigated 136 patients with minor stroke (MS) and transient ischaemic attack (TIA) and found a prevalence of 0·32 for the 4G/4G genotype in patients compared with 0·42 in 115 age-matched healthy controls. The 4G/4G genotype was significantly less frequent among 61 patients symptomatic before the age of 60 years (prevalence 0·20) than in 75 patients symptomatic after 60 years of age (prevalence 0·42; odds ratio). Our results indicate that the 4G/4G genotype is not a risk factor for MS or TIA and may even be protective in young patients. [ABSTRACT FROM AUTHOR]

Background: Gene variants associated with disease could reveal novel mechanisms. We searched for single nucleotide polymorphisms (SNPs) associated with noncardioembolic stroke (nonCES)., Methods: We tested 24,926 SNPs in or near genes for association with nonCES in the Vienna Study (551 cases, 815 controls) and then evaluated the associated SNPs in the UCSF-CC Study (570 cases, 1,604 controls) first in pooled DNA samples and then in individual DNA samples. We then asked whether the risk alleles of the SNPs associated with increased risk in both studies were also associated with increased risk of nonCES in the German Study (728 cases, 1,041 controls)., Results: Six of the 46 SNPs that were associated with nonCES in both the Vienna and the UCSF-CC Studies were also associated with nonCES in the German Study: rs362277 in HTT (OR 1.39, 90% CI 1.12-1.71), rs2924914 near CSMD1 (OR 1.22, 90% CI 1.04-1.43), rs1264352 near DDR1 (OR 1.20, 90% CI 1.02-1.41), rs544115 in NEU3 (OR 1.63, 90% CI 1.02-2.62), rs12481805 in UMODL1 (OR 1.31, 90% CI 1.01-1.81), and rs2857595 near NCR3 (OR 1.15, 90% CI 1.00-1.32). Accounting for multiple testing of 46 SNPs, these 6 SNPs had a false discovery rate of 0.69., Conclusions: Some of the 6 SNPs may be associated with nonCES but most may be false positives. These 6 SNPs merit investigation in additional nonCES study populations., (Copyright © 2011 S. Karger AG, Basel.)

Background: Neurohumoral effects have been suggested to affect kidney function. Stroke is a condition where regulation of the renin-angiotensin system and sympathetic nerve activity are altered., Methods: Renal function as estimated by serum creatinine was analyzed over 1 week in 220 patients after acute ischemic stroke., Results: In patients with chronic kidney disease defined as those with serum creatinine >1.2 mg/dL at admission (n = 62), renal function transiently improved, measured by a mean decrease of creatinine of 0.34 mg/dL during the first days after stroke. A significant and transient decrease of creatinine was also observed in patients with diabetes (n = 69) or patients with heart failure (n = 89). In both subgroups creatinine decreased by a mean of 0.49 and 0.24 mg/dL, respectively (p < 0.05 for both). In patients with normal renal function at admission, no change in serum creatinine occurred during the first week after stroke. There was no association between stroke severity and creatinine change., Conclusion: An acute ischemic cerebrovascular event intermittently improves impaired kidney function. The underlying mechanism may involve central regulation of renal function.

Unlabelled: Overexpression of plasma cell membrane glycoprotein-1 (PC-1) inhibits insulin receptor tyrosine kinase activity and thus favours insulin resistance and atherosclerotic vascular disease. Recent findings indicate that the minor variant K121Q in the PC-1 gene confers an increased risk for early myocardial infarction independent of other established risk factors. We hypothesized that genetic variants in PC-1 may also influence the risk for cerebrovascular disease., Aim: Therefore, we assessed the association of the PC-1 K121Q variant in the coding region and a polymorphism (G2906C) in the 3' untranslated region of the PC-1 gene with the risk of stroke., Patients: We analyzed 1014 patients with a history of ischaemic stroke from the Vienna stroke registry and 1001 control individuals without vascular disease., Results, Conclusion: Genotype frequencies of both genetic variants were similar in patients and controls in the total study population. By multivariate analysis, no interactions were observed between the PC-1 genotype and established vascular risk factors. However, the PC-1 2906C allele was significantly more frequent in patients who suffered from stroke before the age of 40 years. In these patients the risk for ischaemic stroke was increased four-fold.

Data on long-term survival of younger patients with ischemic stroke (IS) are limited. We assessed mortality rates and clinical predictors of survival in patients with IS or transient ischemic attack (TIA) <60 years. Consecutive patients with IS or TIA <60 years admitted to nine neurological departments in Vienna between 1998 and 2001 were included into the current study. The endpoint was overall mortality. Univariate Cox regression analyses were performed. Significant variables after Bonferroni adjustment were further considered in a multivariate Cox regression analysis. Kaplan-Meier curves and ROC curves were plotted. After excluding patients who died within the first 30 days, 661 patients (65% male, mean age 50.2) were followed for a mean of 8.8 years. The cumulative mortality rate was 2.4% after 1 year and 7.8% after 5 years. Diabetes, heavy drinking, heart failure, and age remained significantly associated with mortality in the multivariate Cox regression analysis. Separate analysis of the patient groups <50 and ≥ 50 years showed none of the included factors to be significantly associated with mortality in the younger patient group. In the patient group, ≥ 50 of the same risk factors as in the whole group analysis showed a statistically significant influence. The observed mortality rates were lower compared to earlier studies conducted in younger patient groups. Although we found subgroups at higher risk of death in the entire population, in patients <50 years of age, predictors of survival remained elusive.

Noncardioembolic stroke and coronary heart disease (CHD) may share genetic predispositions. We tested the hypothesis that genetic variants which are associated with risk of CHD would also be associated with risk of noncardioembolic stroke in 562 cases from the Vienna Stroke Registry and 815 controls. We selected 6 gene variants that had been consistently associated with risk of CHD in 3 studies, including the Atherosclerosis Risk in Communities study, and found that 4 of these gene variants were also associated with risk of noncardioembolic stroke. The odds ratios for noncardioembolic stroke were 1.31 (90% CI 1.07-1.60) for rs3900940 in MYH15, 1.24 (90% CI 1.01-1.5) for rs20455 in KIF6, 1.21 (90% CI 0.99-1.49) for rs1010 in VAMP8, and 1.20 (90% CI 0.95-1.50) for rs10757274 on chromosome 9p21., (Copyright 2009 S. Karger AG, Basel.)

Background: Single-nucleotide polymorphisms (SNPs) in inflammation-related genes have been linked to an increased risk of ischemic stroke. Most of these SNP results have not been replicated, however, and metaanalyses of the effects of inflammation-related genes are rare. We investigated 49 SNPs in 34 genes previously reported to be related to inflammation in our study. We tested 459 patients with acute ischemic stroke or transient ischemic attack and 459 controls individually matched by sex and age., Methods: We studied genetic variation by PCR analysis and subsequent hybridization to linear arrays of sequence-specific oligonucleotides. We used univariate conditional logistic regression analysis to test for associations of conventional vascular risk factors and the SNPs with stroke. Variables showing significant differences (P < 0.05) between cases and controls were included in a multivariate model. ROC curves were plotted to assess the contribution of genetic variation to stroke risk in addition to that of conventional risk factors., Results: Univariate regression analysis revealed 3 SNPs with significant allelic differences between patients and controls, which fulfilled the criteria for further analysis. Only one of these SNPs, the C5 (complement component 5) 2416A>G variant (rs17611), remained significant after the multivariate analysis (odds ratio, 0.585; P = 0.0037). ROC curve analysis revealed no contribution of this genetic variation to stroke risk., Conclusions: We found evidence for an association of the 2416A>G polymorphism in the C5 gene with the risk for ischemic stroke. Our data suggest that the C5 gene particularly influences the risk for patients with microangiopathy.

Objective: To elucidate the relationship between excessive daytime sleepiness (EDS) in obstructive sleep apnea (OSA) and carotid atherosclerosis determined by ultrasonography and serum surrogate markers., Methods: One hundred and forty-seven patients (102 males) with snoring and sleep-disordered breathing were investigated. Carotid atherosclerosis was evaluated by serum analysis of high-sensitivity C-reactive protein and fibrinogen and four sonographic indices: intima media thickness (IMT) of the common carotid artery (CCA), IMT from the bulb to the internal carotid artery (ICA), combined IMT measurements from all segments and a plaque score. EDS was assessed by the Epworth Sleepiness Scale (ESS). Pearson correlation analysis, intergroup comparison (ANOVA) and two multiple regression models explored associations between confounders, surrogate markers and EDS., Results: Forty-four patients had no OSA (apnea-hypopnea index AHI<5h(-1)), 27 mild (5-15), 25 moderate (15-30) and 51 severe OSA (>30). The ESS significantly distinguished severe OSA from non-OSA patients (p=0.003). It showed significant correlations with the BMI, HbA1c, systolic RR, the AHI, sleep time spent with an oxygen saturation <90%, the respiratory arousal index, IMT of the CCA and combined IMT measurements, but no correlation with serum markers. The ESS was found to be an independent predictor of CCA-IMT in the pre-polysomnographic multiple regression model (p=0.008), but not in the post-polysomnographic model after including respiratory variables., Conclusion: EDS is associated with obesity, diabetes and all respiratory variables in OSA patients and may serve as an independent predictor of carotid atherosclerosis before polysomnography.

Aim: The aim of the present study was the evaluation of actigraphy as a tool to objectify the recovery process after motor paresis due to stroke., Methods: The motor activity of both arms of patients suffering from stroke was actigraphically recorded at four different time points during the course of rehabilitation: 24-36 h, 5-7 days, 3 months, and 6 months after stroke., Results: Motor activity monitored by wrist-worn actigraphs located at the impaired side revealed an increase in activity between the first two time points and the subsequent ones. Additionally, actigraphic recordings showed lower total motor activity at the impaired side as compared to the nonimpaired side. A significant positive correlation was found between the actigraphically recorded motor activity and the results of the Scandinavian Stroke scale, the Barthel Index, the Rankin Scale Score and with the Motoricity Index during the 1st week, which corresponds to the time when neurological deficits were most pronounced., Conclusion: Our results suggest that actigraphy is a useful tool in the objective evaluation of motor activity after stroke. Moreover, actigraphy covers additional aspects that are not reflected by the usual stroke scales in a clinical situation., (Copyright 2008 S. Karger AG, Basel.)

Background and Purpose: Knowledge about hypertension and its control influences blood pressure control in patients with hypertension. We assessed these parameters in a large cohort of patients with ischemic stroke or transient ischemic attack and analyzed their association with educational attainment., Methods: Five hundred ninety-one consecutive patients with stroke with a medical history of hypertension were interviewed about knowledge concerning hypertension within a multicenter hospital-based stroke registry. We analyzed answers in relation to educational level with multivariate logistic regression adjusted for age and sex., Results: Seventy-seven percent of the patients stated to have known about hypertension being a risk factor for stroke, but only 30% felt at increased risk of stroke. Less than half (47%) could identify 140 mm Hg or less as the maximum tolerated systolic blood pressure, and 53% had their blood pressure only controlled monthly or less often. Knowledge of possible consequences of myocardial infarction, nephropathy, peripheral vascular disease, and retinopathy was 64%, 20%, 11%, and 16%, respectively. Approximately half of patients were acquainted with the nonpharmacologic treatment options of physical activity (49%), reduction of salt intake (54%), and reduction of caloric intake (48%), whereas relaxation techniques were only known to 17%. Adherence to those treatment options ranged from 42% to 67%. Educational level was significantly associated with knowledge of increased risk, possible consequences of hypertension, and knowledge about nonmedication treatment options., Conclusions: Knowledge in our population was insufficient and partly associated with educational level, leaving much room for improvement by educational campaigns. Furthermore, we found a gap between knowledge of the increased risk for stroke in patients with hypertension and awareness of their own risk.

Background: Epidemiological studies indicate that genetic factors play a role in the risk of stroke, particularly in younger individuals, but the role of single-nucleotide polymorphisms (SNPs) is controversial. We tested the possible association of a number of previously described SNPs with stroke risk., Methods: We investigated the prevalence of 60 polymorphisms located in 35 genes in 450 white patients who suffered an acute stroke or transient ischemic attack before the age of 60 years and in 817 healthy control individuals by a multilocus PCR-based assay. The controls were randomly selected from attendees of a health service program. Genetic variations were detected by hybridization to nylon strips (Roche Molecular Systems) containing detection oligonucleotides for the SNPs. We used P values of <0.05 for confirmatory analysis of the SNPs in the genes for APOE (allele 4), angiotensin converting enzyme, factor V, prothrombin, and methylenetetrahydrofolate reductase. To account for multiple testing we defined a P value of <0.001 as statistically significant for all exploratory tests. The genes represented in the test panel by more than 1 SNP were also evaluated by haplotype analysis., Results: Frequencies of all 60 tested SNPs among patients and controls were very similar. No SNP reached an odds ratio of 2, and no association with stroke risk was statistically significant., Conclusions: Our results do not indicate a clinically relevant role of any of the investigated SNPs for stroke risk in individuals hospitalized for ischemic stroke/transient ischemic attack before or at 60 years of age. These results are in accordance with previous metaanalyses showing at most a very modest or no significant effect of these SNPs on stroke risk.

Objectives: We investigated the effect of myeloperoxidase (MPO) on progression of carotid stenosis in states of high and low high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) levels., Background: Myeloperoxidase is pivotally involved in the pathogenesis of atherosclerosis. In vitro data suggest that MPO exerts deleterious effects via oxidative modulation of lipoproteins., Methods: We prospectively studied 1,019 of 1,268 consecutive patients who were asymptomatic with respect to carotid artery disease. Patients underwent serial carotid ultrasound investigations at baseline and after a follow-up interval of median 7.5 months (range 6 to 9 months), categorizing carotid arteries as 0% to 29%, 30% to 49%, 50% to 69%, 70% to 89%, or 90% to 99% stenosed or occluded. The MPO, HDL-C, and LDL-C levels were measured at baseline, grouped by medians, and correlated with progression of carotid atherosclerosis., Results: Progression of carotid atherosclerosis was found in 100 of 1,019 patients (9.8%). Myeloperoxidase (p = 0.014) but not HDL-C (p = 0.95) or LDL-C (p = 0.30) were associated with progressive disease. However, MPO > or =310 ng/ml was significantly associated with progressive disease (adjusted odds ratio [OR] 2.57, 95% confidence interval [CI] 1.39 to 4.75) only in patients with HDL-C levels <49 mg/dl. Otherwise, in patients with higher HDL-C levels (> or =49 mg/dl), MPO > or =310 ng/ml did not predict disease progression (adjusted OR 1.42, 95% CI 0.72 to 2.78). No interaction of MPO with LDL-C was observed., Conclusions: Myeloperoxidase was associated with progression of carotid atherosclerosis in patients with HDL cholesterol levels below 49 mg/dl.

Background: Coagulation factor VII (FVII) plays an important role in the activation of blood coagulation and clot formation. Recent studies have provided evidence for an association between common polymorphic markers in the FVII gene and plasma FVII concentrations. The 353R>Q sequence variation, and 3 common sequence variations in the promoter of the FVII gene-the 10-bp insertion/deletion at position -323 and the -401G>T and -402G>A sequence variations-are well-known determinants of circulating FVII concentrations., Methods: To clarify the role of these sequence variations in the pathogenesis of ischemic stroke, we performed a case-control study with 242 patients with ischemic stroke before the age of 60 years and 239 healthy controls., Results: The -323 insertion/deletion and the 353R>Q and -401G>T sequence variations were in strong linkage disequilibrium, and the resulting haplotypes occurred with equal frequencies in patients and controls. The variant form of FVII (-402G>A) occurred only in combination with the common (wild-type) sequences at all other loci. This haplotype was more frequent in patients than in healthy controls (28% vs 22%). The difference in the prevalence of carriers of this haplotype among patients and controls was statistically significant (P = 0.03; odds ratio = 1.6; 95% confidence interval, 1.1-2.6)., Conclusion: According to our results, the FVII -402A allele seems to increase the risk of early ischemic cerebrovascular events, whereas the 353R>Q, G-401T, and -323ins/del sequence variations, which are in close linkage disequilibrium, apparently do not influence the risk of stroke.

Background: Chronic and acute infections are associated with an increased risk of stroke. The inflammatory response can be influenced by functional polymorphisms in components of the immune system. We hypothesized that these polymorphisms may also modulate the risk of ischemic cerebrovascular events., Methods: We determined the frequency of polymorphisms in tumor necrosis factor-alpha[(TNF-alpha) G(-376)A, G(-244)A, G(-238)A, G(-308)A], Toll-like receptor 4 [(TLR4) Gly299Asp and Thr399Ile], interleukin-1-receptor antagonist [(IL-1-RA) intron 2 variable-number tandem repeat], monocyte differentiation antigen CD14 receptor C(-260)T, and interleukin-6 [(IL-6) G(-174)C] genes in 404 patients with acute stroke or transient ischemic attack before the age of 60 years and in 415 healthy individuals. We also tested for interactions between genotypes, recent febrile episodes and stroke risk., Results: None of the polymorphisms was associated with an increased risk of stroke after adjustment for age and gender. Following multivariate adjustment, carriers of the TNF-alpha (-308)A allele, the IL-1-RA 2* allele or the IL-6 (-174)C allele appeared to have an increased risk of stroke in association with a febrile episode prior to strokes., Conclusion: In our study none of the investigated polymorphisms of the inflammatory system was associated with the risk of acute cerebrovascular events before the age of 60 years. However, post-hoc analyses indicate that some polymorphisms seem to contribute to the risk of stroke in combination with fever.