Lipoprotein lipase Ser447Ter polymorphism associated with the risk of ischemic stroke: a meta-analysis

Introduction

Previous studies suggested lipoprotein lipase (LPL) Ser447Ter and Asn291Ser polymorphisms were associated with the risk of ischemic heart disease, however, their effects on ischemic stroke were controversial. A meta-analysis was performed to assess the associations between these two LPL polymorphisms and the risk of ischemic stroke.

Methods

The electronic databases PubMed and Embase were used to identify relevant studies by two interviews independently. The pooled odds ratios (ORs) and weighted mean differences (WMD) with 95% confidence interval (CI) were estimated for the risk of ischemic stroke and the plasma lipids in various Ser447Ter genotypes respectively. A fixed or random effect model was selected for pooling data based on homogeneity test.

Results

13 studies including 4,681 ischemic stroke cases and 8,516 controls were involved in this meta-analysis. Overall, LPL Ter447 variant was associated with a significantly reduced risk for ischemic stroke (OR = 0.79, 95% CI: 0.68-0.93) both in Caucasian (OR = 0.87, 95% CI: 0.77-0.97) and East-Asian (OR = 0.65, 95% CI: 0.43-0.99), whereas no significant association of Ser291 variant was observed (OR = 1.25, 95% CI: 0.96-1.63). The Ser447Ter polymorphism may be more important in association with the decreased risk of atherosclerotic stroke (OR = 0.44, 95% CI: 0.32-0.62) which derived from significantly increased high density lipoprotein cholesterol, decreased triglyceride and total cholesterol in Ter447 carriers compared with non-carriers.

Conclusions

This meta-analysis indicated that LPL Ser447Ter polymorphism was associated with a significant reduction in the risk of ischemic stroke, especially atherosclerotic stroke subtype in both Caucasian and East-Asian.     

Lack of evidence for association between factor XIII-A Val34Leu polymorphism and ischemic stroke: A meta-analysis of 8,800 subjects

Introduction

Epidemiological studies have evaluated the association between factor XIII-A (FXIII-A) Val34Leu polymorphism and risk of ischemic stroke, but the results remain inconclusive. This meta-analysis was therefore designed to clarify these controversies.

Methods

Systematic searches of electronic databases Embase, PubMed and Web of Science, as well as hand searching of the references of identified articles and the meeting abstracts were performed. Study selection, data abstraction and study quality evaluation (using the Newcastle-Ottawa Scale, NOS) were independently conducted in duplicate. Statistical analyses were performed using software Review Manager (Version 5.1.2) and Stata (Version 11.0). The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were performed. Fixed or random effects model was separately used depending on the heterogeneity between studies. Publication bias was tested by funnel plot, Egger's regression test and Begg's test. Sensitivity analysis was conducted by limiting the meta-analysis to the high quality studies (NOS score≥8).

Results

A total of 16 studies including 3,807 cases and 4,993 controls were combined showing no evidence of association between FXIII-A Val34Leu polymorphism and ischemic stroke (for Val/Leu vs. Val/Val : OR = 0.95, 95%CI = 0.77-1.16; for Leu/Leu vs. Val/Val: OR = 0.90, 95%CI = 0.73-1.11; for dominant model: OR = 0.97, 95%CI = 0.81-1.17; for recessive model: OR = 0.95, 95%CI = 0.77-1.17). In the subgroup analyses by study design, ethnicity and specific subtypes (small-vessel occlusive ischemic stroke and large-artery atherosclerotic ischemic stroke ), there was lack of evidence for the association.

Conclusions

This meta-analysis indicates that there is no evidence for association between factor XIII-A Val34Leu polymorphism and ischemic stroke.     

ABCB1 C3435T polymorphism and risk of adverse clinical events in clopidogrel treated patients: a meta-analysis

Introduction

The ABCB1 C3435T polymorphism limits oral bioavailability of clopidogrel and may influence prognosis of patients treated with clopidogrel. Several studies have examined the association between the C3435T polymorphism and risk of adverse clinical events in clopidogrel treated patients, but the results were inconsistent. To assess the role of the C3435T polymorphism in the impact on clinical outcomes, a meta-analysis was conducted.

Methods

6 studies with 10,153 subjects were included in this meta-analysis. Fixed- or random-effects model was chosen according to heterogeneity. Publication bias was evaluated by fail-safe numbers.

Results

The association of the C3435T polymorphism with risk of overall recurrent ischemic events in clopidogrel treated patients was not statistically significant for all genetic models (OR = 1.13, 95%CI: 0.78-1.64, P = 0.51; OR = 1.15, 95%CI: 0.99-1.33, P = 0.07; OR = 1.19, 95%CI: 0.81-1.76, P = 0.37). Significant association was identified between the C3435T polymorphism and risk of short-term recurrent ischemic events (OR = 1.55, 95% CI: 1.09-2.20, P = 0.01; OR = 1.41, 95% CI: 1.06-1.87, P = 0.02; OR = 1.77, 95% CI: 1.19-2.63, P = 0.005). No statistically significant association between the C3435T polymorphism and stent thrombosis (OR = 0.79, 95% CI: 0.47-1.32, P = 0.37) or bleeding (OR = 0.98, 95% CI: 0.79-1.21, P = 0.82) was identified. The results may be affected by publication bias.

Conclusions

This meta-analysis failed to show an association between the ABCB1 C3435T polymorphism and risk of overall recurrent ischemic events, stent thrombosis or bleeding in clopidogrel treated patients. However, the association between TT homozygotes of the C3435T polymorphism and risk of short-term recurrent ischemic events may exist, but needs more studies to confirm.     

Low protein Z levels but not the protein Z gene G79A polymorphism are a risk factor for ischemic stroke

Background

Protein Z (PZ) is a vitamin K-dependent plasma protein that plays a role in both pro-and anticoagulant pathways, but its exact physiological function remains unclear. The aim of this study was to determine the association between the G79A PZ gene polymorphism in intron F, PZ levels and the occurrence of ischemic stroke.

Methods

We performed a case-control study in 118 Caucasian patients with first ever ischemic stroke or TIA confirmed by CT, and 113 age-and sex-matched population controls. Venous blood samples for PZ levels were collected 7 to 14 days and 3 months after stroke onset. Estimates of relative risk (odds ratios) were adjusted for vascular risk factors.

Results

The adjusted relative risk of ischemic stroke associated with PZ levels in the lowest quartile versus the highest quartile was 3.0 (95% CI: 1.1-8.7) at 7-14 days, and 5.1 (95% CI: 1.2-21.9) at 3 months after the stroke. PZ levels in the convalescent sample were significantly lower than in the acute sample. In the convalescent sample, odds ratios increased with lower quartiles of protein Z level (test for trend p = 0.02). Thirty-nine patients (33%) and 32 (28%) controls were heterozygous for the G79A PZ gene polymorphism and 4 (3%) patients and 4 (4%) controls had the AA-genotype. The PZ levels were significantly lower in subjects with the AA-genotype and intermediate in heterozygote subjects. The odds ratio of ischemic stroke associated with A-allele carriers versus GG-homozygotes was 1.2 (95% CI: 0.7-2.1).

Conclusion

No association between the G79A PZ gene polymorphism and the occurrence of stroke was observed. However, low PZ levels are independently associated with an increased risk of ischemic stroke.     

A case-control study provides evidence of association for a common SNP rs974819 in PDGFD to coronary heart disease and suggests a sex-dependent effect

Introduction

Peden et al. have revealed a significant association between four new risk loci and coronary heart disease (CHD) in Europeans and South Asians. The goal of this study is to evaluate the contribution of these genetic loci to CHD risk in Han Chinese.

Methods

We recruited 161 CHD patients and 112 controls proved by angiography originated from Ningbo in the Eastern China, and performed a case-control association study of the four significant SNPs.

Results

Among the four tested SNPs, we found a significant association of rs974819 in PDGFD gene with CHD (allele p = 0.04; OR = 1.45, 95% CI = 1.02 - 2.08) and the allele A/G of rs974819 shows significant difference in females (allele p = 0.04; OR = 1.83, 95% CI = 1.01 - 3.31). A further meta-analysis showed that rs974819 of PDGFD gene was significantly associated with an increasing risk of CHD (OR = 1.08, 95% CI = 1.05 - 1.11) in both Europeans and South Asians including Han Chinese.

Conclusions

Our findings suggests that rs974819 of PDGFD is also a CHD risk factor in Han Chinese. In addition, it presents a sex-dependent genetic effect.     

Association of PDE4D and IL-1 gene polymorphism with ischemic stroke in a Han Chinese population

Background

The single-nucleotide polymorphisms (SNPs) of the phosphodiesterase 4D (PDE4D) and interleukin-1 (IL-1) genes are associated with increased risk for the development of ischemic stroke (IS) in whites. However, little is known about whether this association could also occur in Han Chinese.

Method

A total of 371 patients with IS and unrelated healthy controls were recruited and the SNPs of the PDE4D (83T/C), (87T/C), IL-1 (−889C/T) and IL-1 (−511C/T) were characterized, respectively, by polymerase chain reactions-restriction fragment length polymorphism (PCR-RFLP). The genotype and allele frequencies of these SNPs in this population were statistically analyzed.

Results

The genotype and allele frequencies of the PDE4D (87T/C) and IL-1 (−511C/T) were similar between IS patients and controls. In contrast, the frequencies of CC genotype and C allele of the PDE4D (83T/C) and the T allele frequency of IL-1 (−889C/T) in IS patients were significantly higher than that in healthy controls (p = 0.001, p = 0.003 and p = 0.02, respectively), independent of the conventional risk factors. The values of odds ratio (OR) reached at OR = 1.603; 95%CI = 1.032-2.489; p = 0.036 for the CC genotype of the PDE4D (83T/C) and OR = 1.913; 95%CI = 1.621-2.375; p = 0.034 for the TT genotype of the IL-1 (−889C/T), respectively.

Conclusions

the SNPs of the PDE4D (83T/C) and IL-1 (−889C/T) were associated with increased risk for the development of IS in Northern Han Chinese.     

The rs11833579 and rs12425791 polymorphisms and risk of ischemic stroke in an Asian population: A meta-analysis

Background

In 2009, a GWAS has confirmed that rs11833579 and rs12425791 near the NINJ2 gene could increase the stroke and ischemic stroke (IS) risk. Recently, several studies have been implemented to assess the relationship between the two SNPs and ischemic stroke risk in Asian. However, the results were poorly consistent. To study the association between the both polymorphisms and the risk of ischemic stroke, we performed a meta-analysis.

Methods

We used odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the strength of association. The heterogeneity was checked by Q test and the inconsistency index (I²). Begg's test and Egger's test were used to assess the possible publication bias.

Results

Our study included 6 articles, contained 9 independent case-control studies, involved a total of 9,142 cases and 10,652 controls about rs11833579, 10,165 cases and 11,592 controls about rs12425791. There was a significant association between rs12425791 and IS risk with dominant genetic model (OR = 1.087, 95%CI = 1.021-1.158, I² = 34.6%, P = 0.152), but not with recessive genetic model and allele A vs. allele G. For rs11833579, we failed to verify it relate with IS risk under allele A vs. allele G, dominant and recessive genetic model.

Conclusions

This meta-analysis suggest that rs12425791 is relative to ischemic stroke risk under dominant model in Asian population, but not for rs11833579.     

Gender differences in the effects of peroxisome proliferator-activated receptor γ2 gene polymorphisms on metabolic adversity in patients with schizophrenia or schizoaffective disorder

Objective

Metabolic syndrome (MS) is a major health problem in schizophrenic patients. Peroxisome proliferator-activated receptor γ2 (PPARγ2) is one of the candidate genes responsible for the liability to metabolic problems. In this study, we investigated the effect of the PPARγ2 gene Pro12Ala and C161T polymorphisms on metabolic adversities in patients with schizophrenia or schizoaffective disorder.

Methods

Metabolic profiles and PPARγ2 gene polymorphisms were determined in 600 patients (309 men and 291 women) with a clinical diagnosis of schizophrenia or schizoaffective disorder. Metabolic indices and components of MS were compared between patients with different Pro12Ala or C161T genotypes.

Results

In the whole population, the allele frequency of 12Ala and 161T was 4.4% and 24.7% respectively. Both polymorphisms had no significant effect on obesity or metabolic-related traits. However, following gender stratification of the data, we found female 12Ala allele carriers were at greater risk of developing abdominal obesity (OR = 4.0, 95% CI = 1.1-14.2, p = 0.04) and hypertension (OR = 2.9, 95% CI = 1.2-7.4, p = 0.02) than female 12Ala allele non-carriers. Male 161T allele carriers had lower insulin levels (p = 0.02) and lower high-density lipoprotein cholesterol (HDL-C) (p = 0.05) levels than male 161T allele non-carriers. Moreover, female 161T allele carriers had higher body weight (p = 0.04), waist circumference (p = 0.05), and systolic blood pressure (p = 0.01), and were at greater risk of developing hypertension (OR = 2.0, 95% CI = 1.1-3.5, p = 0.02). Haplotype analyses showed that PPARγ2 gene polymorphisms were significantly associated with HDL-C level in men and blood pressure in women.

Conclusions

We did not find an association of PPARγ2 gene polymorphisms with MS or obesity in our schizophrenia sample. But further analyses by gender stratification revealed gender-specific differences in the effect of different PPARγ2 genotypes on certain metabolic adversities in these patients.     

Acute ischemic stroke in the very elderly Chinese: risk factors, hospital management and one-year outcome

Background

Little information is available on Asian patients over 80 years with stroke. We aimed to investigate characteristics of the very elderly ischemic stroke hospitalized patients in China.

Methods

We prospectively enrolled consecutive patients with acute ischemic stroke from March, 2002 to October, 2008 into the analysis. Patients were divided into two groups: <80 years versus ≥80 years and risk factors, hospital management and one-year outcome were compared.

Results

Of the 2619 cases included, 302 (11.5%) patients were 80 years or older. Compared with patients <80 years, patients over 80 years old had higher rates of hypertension (66.2% versus 56.1%, p = 0.001), atrial fibrillation (23.5% versus 14.5%, p = 0.000), and coronary heart disease (13.6% versus 5.7%, p = 0.000). In addition, they were less likely to have received transthoracic echocardiography (45.4% versus 55.4%, p = 0.001), color Doppler of extracranial vessels (54.0% versus 61.2%, p = 0.015), antiplatelet agents (80.8% versus 86.8%, p = 0.004), or anticoagulants (4.0% versus 9.0%, p = 0.003). After adjusting for sex and stroke severity on admission, the very elderly patients had higher case-fatality and disability rates at one year (33.8% versus 13.2%, p = 0.000; 37.8% versus 20.9%, p = 0.000; respectively).

Conclusions

In China, the proportion of the very elderly in hospitalized stroke population is lower than that in western countries whereas the most common risk factors seem similar. The hospital management for these patients is relatively insufficient and the long-term outcome is generally unfavorable compared with patients under 80 years old.     

The impact of co-morbid conditions on family history of venous thromboembolism in Whites and Blacks

Introduction

Our objectives were to compare the magnitude of family history as a risk factor for venous thromboembolism (VTE) risk between Blacks and Whites, and to assess the impact of co-morbid conditions on familial risk for VTE.

Materials and methods

We used data from the Genetic Attributes Thrombosis Epidemiology (GATE) study, a matched case-control study which enrolled Blacks and Whites aged 18-70 years in Atlanta, Georgia. A total of 1,094 case patients with a deep vein thrombosis (DVT) or pulmonary embolism (PE) and 1,264 control patients were interviewed about their family history.

Results

Family history of VTE was a statistically significant risk factor for VTE among Blacks (odds ratio (OR) = 2.9, 95% confidence interval (CI) 2.0-4.1; P value < 0.0001) and among Whites (OR = 2.7, 95% CI 1.9-3.7; P value < 0.0001); among Blacks and Whites who were obese or had hypertension; among Blacks who had diabetes mellitus or cancer; as well as among males and females, and across all age categories. Family history of VTE increased the risk of VTE among Blacks with cancer by about 6-fold, whereas among Blacks without cancer the increased risk due to a positive family history was about 3-fold; a 2-fold relative difference. In addition, family history was a risk factor for VTE among case patients with DVT only or with PE only. The effect of family history generally was stronger among those with recurrent episodes of VTE compared with a first episode of VTE. For example, family history of any VTE was a strong risk factor among Black females with recurrent VTE compared with Black females with first VTE (OR = 3.9, 95% CI 2.0-7.5; P value < 0.0001).

Conclusion

Our study indicated that the adjusted attributable fraction for VTE was 16.9% among Blacks vs. 18.3% among Whites, and certain co-morbid conditions could further increase the risk of VTE associated with a positive family history of VTE.     

A pilot study of antipsychotic prescribing decisions for acutely-Ill hospitalized patients

Background

Evidence on antipsychotic prescribing decisions is limited. This pilot study quantified factors considered in choosing an antipsychotic and evaluated the influence of metabolic status on treatment decisions.

Methods

Prescribing decisions by 4 psychiatrists were examined based on 80 adult patients initiated on antipsychotic medication diagnosed with schizophrenia, schizoaffective disorder or bipolar disorder by DSM-IV criteria, who were admitted to an acute inpatient psychiatric program of an urban Veterans Affairs Medical Center. The primary analysis examined the association between antipsychotic treatment choice and predictions of symptom control and metabolic risk. Secondary analyses included comparison of the chosen and next best treatments in predicted symptom control and metabolic risk, the frequency of reasons cited for drug choice, and the association between treatment choice and patients' baseline metabolic parameters. Mean differences and odds-ratios (OR) with 95% confidence intervals were used to compare relationships between treatment choice, ratings of risk and metabolic data.

Results

Antipsychotic choice correlated significantly with ratings of predicted symptom control (OR = .92, p = 0.02) and metabolic risk (OR = .88, p = 0.01). Mean differences between the chosen and next best drugs were significant but small in predicted symptom control (F = 2.81, df = 3, 76; p < 0.05) compared with larger differences in anticipated metabolic risk (F = 14.80, df = 3, 76; p = 0.0001). Nevertheless, among 24 identified reasons influencing drug selection, anticipated metabolic risk of chosen antipsychotics was cited less often than efficacy measures. In contrast to psychiatrists' expectations of metabolic risk with selected treatments, we found that patients' actual baseline BMI, fasting glucose, blood pressure, and Framingham risk levels did not necessarily predict antipsychotic treatment choice independent of other factors.

Conclusion

In the context of an acute psychiatric hospitalization, pilot data suggest that predictions of symptom control and metabolic risk correlated significantly with antipsychotic choice, but study psychiatrists were willing to assume relative degrees of metabolic risk in favor of effective symptom control. However, prescribing decisions were influenced by numerous patient and treatment factors. These findings support the potential utility of the ATCQ questionnaire in quantifying antipsychotic prescribing decisions. Further validation studies of the ATCQ questionnaire could enhance translation of research findings and application of treatment guidelines.     

Plasma factor and inhibitor composition contributes to thrombin generation dynamics in patients with acute or previous cerebrovascular events

Introduction

More than 80% of cerebrovascular events are ischemic and largely thromboembolic by nature. We evaluated whether plasma factor composition and thrombin generation dynamics might be a contributor to the thrombotic phenotype of ischemic cerebrovascular events.

Materials and Methods

We studied (1) 100 patients with acute ischemic stroke (n = 50) or transient ischemic attack (TIA) (n = 50) within the first 24 hours from symptom onset, and (2) 100 individuals 1 to 4 years following ischemic stroke (n = 50) or TIA (n = 50). The tissue factor pathway to thrombin generation was simulated with a mathematical model using plasma levels of clotting factors (F)II, V, VII, VIII, IX, X, antithrombin and free tissue factor pathway inhibitor (TFPI).

Results

The plasma levels of free TFPI, FII, FVIII, and FX were higher, while antithrombin was lower, in the acute patients compared to the previous event group (all p ≤ 0.02). Thrombin generation during acute events was enhanced, with an 11% faster maximum rate, a 15% higher maximum level and a 26% larger total production (all p < 0.01). The increased thrombin generation in acute patients was determined by higher FII and lower antithrombin, while increased free TFPI mediated this effect. When the groups are classified by etiology, all stroke sub-types except cardioembolic have increased TFPI and decreased AT and total thrombin produced.

Conclusion

Augmented thrombin generation in acute stroke/TIA is to some extent determined by altered plasma levels of coagulation factors.     

Haplotypes of the endothelial protein C receptor gene and Behçet's disease

Introduction

Behçet's disease is a vasculitis of unknown cause in which thrombosis occurs in about 25% of patients. Two haplotypes of the endothelial protein C receptor gene, H1 and H3, are associated with the risk of thrombosis. Thus, the objective of this study was to evaluate the influence of these haplotypes on the thrombosis risk in Behçet's disease.

Material and Methods

We evaluated the H1 and H3 haplotypes in 87 patients with Behçet's disease, 19 with and 68 without a history of thrombosis, and in 260 healthy individuals. We also measured protein C, activated protein C, and soluble endothelial protein C receptor levels in all individuals.

Results

The presence of the H1 haplotype seemed to protect Behçet's patients against thrombosis (odds ratio 0.21; 95% CI 0.1-0.8; p = 0.023), whereas the frequency of the H3 haplotype was lower in patients than in control individuals (0.19; 0.1-0.5; p = 0.006). Furthermore, the H1 haplotype was associated with increased levels of activated protein C, whereas the H3 haplotype was associated with the highest soluble endothelial protein C levels. Moreover, activated protein C levels were lower in patients with than in patients without posterior uveitis (p < 0.001).

Conclusions

These findings indicate that the H1 haplotype protects Behçet's patients from thrombosis, likely via increased levels of activated protein C, whereas individuals carrying the H3 haplotype seem to be protected from the clinical manifestations associated with Behçet's disease, probably via increased soluble endothelial protein C levels.     

Hopelessness, a potential endophenotpye for suicidal behavior, is influenced by TPH2 gene variants

Objectives

Hopelessness is one of the strongest risk factors for suicidal behavior but relevant genetic studies are poorly available. Tryptophan hydroxylase (TPH) is widely considered to be a good candidate for genetic association studies on depression and suicide, however, investigations on these complex, multifactorial phenotypes have resulted in conflicting data. We hypothesized that hopelessness could be a mediating phenotype between TPH2 gene, depression and suicidal behavior.

Methods

Depressive phenotype and suicidal risk were investigated of 760 individuals from general population by Zung Self Rating Depression Scale (ZDS), Beck's Hopelessness Scale (BHS) and a detailed background questionnaire. All participants' DNA samples were genotyped for 7 tag SNPs in TPH2 gene. Generalized linear models were performed for single marker association studies and p-values were corrected by Bonferroni criteria. In haplotype analyses score tests were used and permutated p-values were computed.

Results

Four SNPs of TPH2 gene showed association with hopelessness but only rs6582078 had a significant effect on the BHS scores after Bonferroni's correction; GG individuals had significantly higher BHS scores, while GT and TT had intermediate and lower BHS scores respectively (p = 0.0047). Compared with other genotypes, homozygous GG individuals also had almost three times greater estimated suicidal risk, as did carriers of the AA genotype of rs6582078 (OR = 2.87; p = 0.005) and also of rs1352250 (OR = 2.86; p = 0.006). A risk and a protective haplotype of TPH2 gene were also identified in association with hopelessness. ZDS scores have not shown any association with TPH2 gene.

Conclusions

We found that hopelessness, with its allied increased suicidal risk was strongly associated with TPH2 gene variants in multiple tests. These findings suggest that TPH2 gene confers risk for suicidal behavior while hopelessness can be a potential endophenotype for suicidal vulnerability.     

Suicidality in temporal lobe epilepsy: measuring the weight of impulsivity and depression

Objective

The aim of the work described here was to measure the role of psychopathological features, specifically impulsivity and depression, in suicidality in patients with temporal lobe epilepsy (TLE).

Methods

Neuropsychiatric evaluation of 66 outpatients with TLE was performed with the following instruments: a structured clinical interview (Mini International Neuropsychiatric Interview Plus), the Barratt Impulsiveness Scale, the Hamilton Anxiety Scale, the Beck Depression Inventory, and the Brief Psychiatric Rating Scale.

Results

A current Axis I psychiatric diagnosis, mainly mood and anxiety disorders, was assigned to 37 subjects (56.1%) Presence of suicide risk was identified in 19 patients (28.8%), and 14 (21.2%) had attempted suicide. Frequency of seizures (P = 0.012), current major depression (P = 0.001), and motor impulsivity (P = 0.005) were associated with suicide risk on univariate analysis. Logistic regression stressed the main relevance of major depression (OR = 12.82, 95% CI = 2.58-63.76, P = 0.002) and motor impulsivity (OR = 1.21, 95% CI = 1.06-1.38, P = 0.005) to suicide risk.

Conclusion

Depression has a major influence on suicidality in epilepsy. Motor impulsivity is also relevant and may be an important component of depression in TLE associated with suicide risk.     

Eosinophil count predicts mortality following percutaneous coronary intervention

Introduction

Several inflammatory markers have been shown to be independent predictors for both the development of clinically significant atherosclerosis and for adverse outcome in patients with symptomatic coronary artery disease (CAD). We investigated the prognostic role of eosinophil count in low to intermediate risk patients with CAD.

Methods

We studied 909 patients admitted for elective or urgent percutaneous coronary intervention (PCI) from April 2002 to December 2004, and measured pre-procedural total and differential white blood cell (WBC) counts. Inter-tertile WBC differences in short (6 months) and long term (up to 74 months) mortality were analysed after adjusting for differences in baseline characteristics.

Results

Over a median period of 54 months (inter-quartile range 47-65), a total of 138 deaths (15.2%) occurred, of which 24 were in the first 6 months of follow-up. Cox regression analysis showed that high pre-procedural eosinophil count (top tertile) was associated with improved outcome within the first 6 months (OR = 0.23 [0.06-0.84]; p = 0.03) but after this period there was an increased risk of mortality (OR = 2.21, [1.26-3.88]; p = 0.006).

Conclusions

Eosinophil count is a novel biomarker for risk stratification of CAD patients, which was associated initially with reduced mortality, but after 6 months with increased mortality.     

Aspirin non-responder status and early neurological deterioration: a prospective study

Objectives

In acute ischemic stroke, early neurological deterioration (END) has a severe impact on patient outcome. We tested the hypothesis that initial biological aspirin non-responder status (ANRS) helps predict END.

Methods

A total of 85 patients with acute ischemic stroke on 160 mg aspirin daily were prospectively included. END was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) ≥4 points in the first 72 h after admission. Platelet responsiveness to aspirin was assessed using the PFA-100 system, and ANRS was defined as a collagen/epinephrine closure time <165 ms.

Results

END was observed in 10 patients (11.8%). The presumed reasons for END were progressive stroke (40%), recurrent cerebral ischemia (30%), malignant middle cerebral artery infarction (20%) and secondary acute hydrocephalus (10%). Patients with END had a non-significant worse neurological status on the NIHSS at hospital admission (8.4 vs. 4.2; p = 0.15). Initial impaired consciousness (30% vs. 3%), visual disturbance (60% vs. 23%) and ANRS (60% vs. 20%) were observed more frequently in patients with END. In multivariate analysis, impaired consciousness (OR: 17.3; 95% CI: 2.0-149.5; p = 0.01) and ANRS (OR: 6.4; 95% CI: 1.4-29.6; p = 0.017) were found to be independently associated with END.

Conclusion

ANRS is common in acute ischemic stroke patients and is predictive of END. The clinical significance of these findings requires further evaluation in larger longitudinal studies.     

No evidence for an association between ABO blood group and overall ischemic stroke or any of the major etiologic subtypes

Introduction

The ABO blood group system is encoded by one gene, ABO. Previous studies have reported an association between blood group non-O (i.e. phenotype A, B or AB) and myocardial infarction. Studies on stroke and ABO are, however, more scarce. Therefore, we aimed to investigate whether ABO phenotype or genotype is associated with ischemic stroke and/or etiologic subtypes of ischemic stroke.

Materials and methods

The study was performed in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), which comprises 600 patients with ischemic stroke before the age of 70 years, and 600 matched controls. Patients were classified according to the TOAST criteria.

Results

There was no significant association between ABO phenotype (blood group O vs. non-O) and overall ischemic stroke (multivariable odds ratio of 0.9, 95% confidence interval 0.7-1.2). This was also true for blood group O vs. A and O vs. B. Furthermore, no association between ABO genotypes and ischemic stroke was detected. The ischemic stroke subtype analysis was confined to large-vessel disease, small-vessel disease, cardioembolic stroke and cryptogenic stroke. In this analysis, there was no significant association between any ischemic stroke subtype and ABO phenotype or genotype.

Conclusions

The findings in this study suggest that ABO phenotype or genotype does not have a major impact in the pathophysiology of ischemic stroke or any of the ischemic stroke subtypes.     

Circulating activated factor XI and active tissue factor as predictors of worse prognosis in patients following ischemic cerebrovascular events

Background

Elevated factor (F)XI is associated with an increased risk for ischemic stroke. Activated FXI (FXIa) and tissue factor (TF) have not been studied following stroke. The aim of the current study was to evaluate circulating FXIa and TF in patients with prior cerebrovascular events.

Patients/Methods

We studied 241 patients, including 162 after ischemic stroke and 79 after transient ischemic attack (TIA), recruited 6 months to 4 years (median, 36 months) after the events. Plasma TF and FXIa activity following the index event were determined in clotting assays by measuring the response to inhibitory monoclonal antibodies.

Results

Active TF was detected in 25 (10.4%) of the patients, while FXIa activity (median, 37.5 [IQR 397] pM) was found in 64 (26.7%) of the patients (p < 0.01). The prevalence of active TF and FXIa was higher in subjects with previous stroke compared with those with a history of TIA (13% vs 5.1%, p = 0.05, and 34% vs 11.4%, p < 0.0001, respectively). Patients with circulating FXIa were younger and had higher fibrinogen and interleukin-6 compared to the remainder. Patients with detectable TF or FXIa activity had higher NIHSS score, higher modified Rankin scale and lower Barthel Index than the remaining subjects (all p < 0.05).

Conclusion

Circulating active TF and FXIa can occur in patients with cerebrovascular ischemic events ≥ 6 months after the events. The presence of these factors is associated with worse functional outcomes, which highlights the role of persistent hypercoagulable state in cerebrovascular disease.     

Lack of association between TLR4 Asp299Gly polymorphism and atherosclerosis: evidence from meta-analysis

Introduction

Toll like receptor 4 (TLR4) expression was found to increase markedly in human atherosclerotic lesions, notably on macrophages and endothelial cells. TLR4 Asp299Gly polymorphism was associated with a blunted receptor activity and a subsequently diminished inflammatory response, and may subsequently reduce atherosclerosis (AS) risk. However, the results of molecular epidemiological studies remained inconsistent.

Materials and methods

The PubMed, CNKI databases were searched for all articles available. The OR corresponding to the 95% confidence interval (95% CI) was used to assess the association between TLR4 Asp299Gly polymorphism and risk of AS.

Results

15 case-control studies with 9,989 cases and 6,746 controls were available for this analysis. For control subjects, G allele frequency of TLR4 Asp299Gly polymorphism was ranging from 0.045 to 0.085. The G allele and the AG/GG genotypes were not associated with significantly risk of AS (OR = 1.02, 95% CI = 0.83 - 1.26 for G versus A and OR = 0.96, 95% CI = 0.80 - 1.15 for AG/GG versus AA, respectively) by random effects model.

Conclusion

These findings indicated that TLR4 Asp299Gly polymorphism may not play a role in AS development.