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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It was the aim of this study to determine the associations of clinical and laboratory data with plasma homocyst(e)ine levels in patients with transient ischemic attack (TIA) or minor stroke (MS), with special reference to their 677C to T mutation status in the 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR) gene. Seventy-six patients with TIA or MS were investigated at least 3 months after their (last) clinical event. By means of univariate analysis, significant correlations of homocyst(e)ine levels with male gender (P<0.02), age (P<0.0005), creatinine levels (P<0.0002), folate levels (inversely, P<0.05), and alcohol use (P<0.02) were found, but not with vitamin B12 levels. Multivariate regression analysis, including age, creatinine levels, and folate levels as independent variables, revealed age (P<0.01) and creatinine levels (P<0.02) to be significantly correlated with homocyst(e)ine levels. After adjustment for age, creatinine levels and homocyst(e)ine levels remained significantly correlated to each other (P<0.005), whereas the relation between folate levels and homocyst(e)ine levels was no longer significant (P=0.10). Mutation-positive patients exhibited moderately and statistically non-significantly higher homocyst(e)ine levels than mutation-negative patients, particularly those who were homozygous positive. Homocyst(e)ine levels were closely correlated with creatinine levels (P<0.0002) and with folate levels (inversely, P<0.05), but only in mutation-positive and not in mutation-negative patients. Homozygous positive, heterozygous positive, and mutation-negative patients did not differ with respect to clinical and laboratory data concerning 'risk factors for stroke' or co-existing vascular disease. In conclusion, the associations of creatinine levels and, inversely, of folate levels with plasma homocyst(e)ine levels in patients with TIA or MS are dependent on the 5,10-MTHFR mutation status. Significant correlations between these variables were found only in mutation-positive but not in mutation-negative patients.
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PMID:677C to T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and plasma homocyst(e)ine levels in patients with TIA or minor stroke. 956 60

A common C677T mutation in the gene for the enzyme 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR) has been linked to elevated levels of homocysteine and was therefore suspected to be a candidate genetic risk factor for arterial occlusive disease. Another mutation, factor V Leiden, has been established as a common hereditary risk factor for venous thrombosis, but its role in arterial disease remains controversial. We investigated the prevalence of both the C677T MTHFR mutation and the factor V Leiden mutation in 81 patients with transient ischemic attack (TIA) or minor stroke (MS) and in 81 age- and sex-matched control subjects free from clinically manifest vascular disease. We further compared clinical and laboratory data as well as clinical course of patients carrying the factor V Leiden mutation alone or in combination with the C677T MTHFR mutation and mutation-free patients. The prevalence of the MTHFR mutation did not differ between patients and control subjects with 11.1% homozygous carriers in both groups (OR for homozygous carriers 1.0; 95% CI 0.38-2.66). However, there was a trend towards a higher prevalence of carriers of factor V Leiden in patients (12.3%) than in control subjects (4.9%) (OR 2.75; 95% CI 0.83-9.17;p=0.09). Furthermore, we found some evidence that the combined occurrence of the C677T MTHFR mutation and factor V Leiden might unfavorably affect the clinical course of the disease, but the number of respective patients was small. Larger studies with a greater number of carriers of both the C677T MTHFR mutation and factor V Leiden seem therefore warranted.
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PMID:C677T MTHFR mutation and factor V Leiden mutation in patients with TIA/minor stroke: a case-control study. 995 Feb 59

Ischaemic stroke is a rare occurrence in children and in a proportion of cases the aetiology remains unknown. We have investigated the role of thrombophilia in the aetiology of this condition. Of 50 cases identified at two centres, 37 were available for detailed haematological analysis. No cases were identified with deficiencies of antithrombin, protein C or protein S. One case had elevated IgG anticardiolipin antibodies at low titre. The prevalence of the prothrombin 20210 G-->A mutation, factor V Leiden (FVL) mutation and the C677T mutation in the MTHFR gene was compared in cases to that observed in random unselected cord blood controls. The odds ratio for stroke was not significantly increased in carriers of the prothrombin mutation (OR 1.2; 95% CI 0.1-10.7), FVL (OR 2.5; 95% CI 0.5-13.5), or the C677T mutation (OR 1.7; 95% CI 0.6-4.5). Our findings suggest that thrombophilia may not play a significant role in the aetiology of stroke in children, although a large prospective study is required to investigate this area further.
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PMID:Factor V Leiden, prothrombin 20210G-->A and the MTHFR C677T mutations in childhood stroke. 1036 38

The balance of evidence from observational studies suggests that elevated homocysteine levels are associated with increased risk of carotid artery disease and stroke. There is however a paucity of prospective studies. There are also concerns regarding confounding due to factors associated with hyperhomocysteinemia, including renal impairment, an atherogenic diet and cigarette smoking. Homozygosity for a defective thermolabile variant of MTHFR, a common genetic polymorphism which results in hyperhomocysteinemia, has not been consistently linked with stroke or other vascular disease. There is a need for additional prospective studies with data on relevant confounders, sufficient power to characterise the form of the association between homocysteine concentrations and stroke risk, whether linear or threshold, and power to study interactions between homocysteine, other dietary markers and established stroke risk factors such as smoking and hypertension. Similarly, the evidence linking hyperhomocysteinemia with hypertension is limited and inconsistent. Given the biological mechanisms proposed in support of the homocysteine-CVD hypothesis, one would predict a positive association between homocysteine and blood pressure. There is a need to address this hypothesis directly in studies with reliable measurements of both homocysteine and blood pressure. Ultimately, the case for a causal role for elevated homocysteine levels in vascular disease, including hypertension and stroke, will depend on data from randomised controlled trials of homocysteine lowering interventions. Given the high prevalence of hyperhomocysteinemia in apparently well nourished populations and the tendency for homocysteine concentrations to increase with age, modest effects of homocysteine on stroke risk will have profound implications for public health.
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PMID:Homocysteine, hypertension and stroke. 1037 45

Hereditary thrombophilias are a heterogenous group of genetic coagulation disorders which, particularly in combination with acquired prothrombotic factors, induce a predisposition to thrombosis. After characterization of frequent thrombophilic syndromes like factor V-Leiden or the prothrombin 20210GA mutation, a number of case-control studies screened for the prevalence of these mutations in ischemic stroke and cerebral venous thrombosis (CVT). Our meta-analysis shows that factor V-Leiden and prothrombin are frequent and significantly associated with CVT (16.4% vs. 4.9% or 4.3, P < 0.001, and 12.1% vs. 1.9% or 5.8, P < 0.001). In ischemic stroke, only factor V-Leiden and not prothrombin is a weak but significant risk factor (5.9% vs. 2.6% or 1.6, P < 0.001, and 4.1% vs. 3.3% or 1.4, P = 0.1). The C677T homozygous point mutation in the MTHFR, a homocysteine-degrading enzyme, was also associated with arterial stroke (16% vs. 15% or 1.5, P < 0.001). For CVT, sufficient data are lacking. We therefore recommend screening for thrombophilia in CVT. In ischemic stroke, atrial premature complex (APC) resistance should be considered. As long as controlled studies are lacking, individual anticoagulant therapy must take hereditary and precipitating factors into account to assess potential thrombotic risk.
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PMID:[Hereditary thrombophilia with ischemiC stroke and sinus thrombosis. Diagnosis, therapy and meta-analysis]. 1113 89

In this study of 118 children (median age 5.1 years; range 6 months to 17 years) with ischaemic stroke or transient ischaemic attack (TIA), 22 children (19%) were homozygous for the thermolabile variant of the methylenetetrahydrofolate reductase allele (t-MTHFR), compared with nine of 78 (12%) of a reference population (p=0.18, OR 1.76, 95% CI 0.76 to 4.04). Of those with cerebrovascular disease (CVD), 17 of 84 were homozygous for the t-MTHFR allele (p=0.13 compared with the reference population (OR 1.95, 95% CI 0.81 to 4.65). There was a significant (p<0.025) increment of plasma total homocysteine concentration in homozygotes for the t-MTHFR allele compared with heterozygotes, negatives for the t-MTHFR allele, and control children with no history of stroke. In four of 12 homozygotes for the t-MTHFR allele, plasma homocysteine levels were raised, compared with three of 38 of those who were negative or heterozygous (p=0.047; OR 5.8, 95% CI 1.1 to 31.2). Homozygotes for the t-MTHFR allele were significantly more likely to have a recurrent event than those who were negative or heterozygous (Cox regression p=0.031, hazard ratio 2.18, 95% CI 1.08 to 4.42). These data suggest that homozygosity for the t-MTHFR allele is associated with raised homocysteine levels in children and is a risk factor for primary and secondary stroke and TIA.
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PMID:Homozygous thermolabile variant of the methylenetetrahydrofolate reductase gene: a potential risk factor for hyperhomocysteinaemia, CVD, and stroke in childhood. 1130 98

Although controversial, data on the genetic polymorphism of apoprotein E (APOE), methylenetetrahydrofolate (MTHFR) and paraoxonase (PON1) genes implicate their role in the development of cerebrovascular disease. The aim of this study was to assess the association of polymorphism of APOE, MTHFR and PON1 genes in 56 stroke and 36 carotid stenosis patients, and in 124 control subjects by PCR-restriction fragment length polymorphism analysis. In the stroke group a significantly different MTHFR genotype distribution (p=0.004, odds ratio for T/T of 17.571), but no significant difference in APOE and PON1 allele and genotype distribution compared to the control was found. The carotid stenosis group exhibited a significantly different APOE allele and genotype distribution (p=0.023, odds ratio APOEepsilon3epsilon4 of 4.24), but no significant difference in the MTHFR and PON1 allele and genotype distribution from the control group. The preliminary results obtained in this study revealed an association of the MTHFR and APOE gene polymorphism with cerebrovascular disease, suggesting a significant risk for stroke in subjects who are homozygous for the T allele and for carotid stenosis in subjects having APOEepsilon3epsilon4 genotype. Additional studies in larger patient groups are needed to confirm these observations.
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PMID:Polymorphism of apoprotein E (APOE), methylenetetrahydrofolate reductase (MTHFR) and paraoxonase (PON1) genes in patients with cerebrovascular disease. 2463 86

Currently, the established risk factors for cardiovascular disease (CVD) are largely environmental in nature. Conflicting studies have suggested that mutations in specific coagulation genes may also provide a genetic basis for CVD risk. We reviewed clinical studies that examined the role of single nucleotide polymorphisms in coagulation and platelet factors, and a biochemical factor to determine if specific genotypes are correlated with patients with a history of arterial thrombotic diseases (acute coronary syndromes or stroke). A meta-analysis was performed on studies for factors II (G20210A variant), V Leiden (G1691A), VII (R353Q), glycoprotein (GP) IIIa receptor (PI(A1/A2)), and methylenetetrahydrofolate reductase (MTHFR, C677T). There was no correlation for factor II or factor V polymorphisms to coronary artery disease (CAD) in 5,607 and 5,431 patients studied, respectively. There was also no correlation for factor II variants and stroke in 3,451 patients studied. For factor V, statistical significance was achieved for the G1691A variant on 3,399 patients with stroke (odds ratio [OR] 1.43, 95% confidence intervals [CI] 1.03 to 1.97). The GP IIIa PI(A1/A2) genotype was associated with increased risk for CAD in 7,920 patients (OR 1.12, 95% CI 1.01 to 1.24), but not for 1,855 patients who had a stroke (OR 0.80, 95% CI 0.62 to 1.04). The combined RQ and RR genotypes of factor VII R353Q were correlated to a reduced risk for CVD in 2,574 patients (OR 0.78, 95% CI 0.65 to 0.93), whereas the QQ genotype had offered more protection (OR 0.53, 95% CI 0.27 to 1.03). The TT homozygous variant of MTHFR was associated with CAD risk in 5,644 patients studied (OR 1.30, 95% CI 1.11 to 1.52) but not for 3,075 patients with stroke. This study shows that for some genes, further studies are unnecessary, whereas for others, no more enrollments are needed. The impact of certain genotypes must be examined in relation to other established risk factors and potentially new therapeutic strategies.
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PMID:Correlation of polymorphisms to coagulation and biochemical risk factors for cardiovascular diseases. 1139 54

We present data on the known risk factors encountered in children presenting with a first arterial ischemic stroke to a single tertiary center over 22 years. Two hundred twelve patients (54% male; median age, 5 years) were identified. One hundred fifteen (54%) were previously healthy. Cerebral arterial imaging was undertaken in 185 patients (87%) and was abnormal in 79%. Of 104 previously healthy patients investigated with echocardiography, only 8 had abnormal studies. Genetic or acquired conditions causing thrombophilia were rare. Forty percent of patients were anemic, and 21% either had elevated total plasma homocysteine or were homozygous for the t-MTHFR mutation. Trauma and previous varicella zoster infection were significantly more common in the previously healthy group. There was a significant association between cerebral arterial abnormalities and systolic blood pressure greater than 90th percentile and a trend for an association with varicella within the previous year. Clinical history and examination usually identify underlying risk factors and precipitating triggers for arterial ischemic stroke in childhood. Cerebral arterial imaging is usually abnormal, but echocardiography and prothrombotic screening are commonly negative.
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PMID:Investigation of risk factors in children with arterial ischemic stroke. 1255 79

Atherosclerosis is an important medical problem of the 21st century, but traditional risk factors could only account for 50% of the problem. Hyperhomocysteinemia is emerging as an independent atherosclerosis risk factor, associated with folate deficiency, renal failure, and relative deficiency of MTHFR (C677T polymorphism) or other enzymes depending on gender, age, and smoking status. Hyperhomocysteinemia has been reported to occur in 11-22% of western people, in 3-5% of normal asymptomatic Chinese subjects aged 18-70 years in Hong Kong, Macau, Sydney, and San Francisco, 23-36% of Chinese in Hong Kong with premature coronary artery disease, and 29% of a nonselective series of coronary subjects in Hong Kong. Evidence is accumulating that documents its associations with atherosclerosis disease in both case-control observations and prospective cohort studies, in vitro experiments, and in vivo experimental models in both animals and human subjects, as well as the successful improvement by homocysteine-lowering of endothelial function as surrogate atherosclerosis endpoints in asymptomatic human and coronary patients (secondary prevention). A number of large scale homocysteine-lowering trials are currently underway for stroke and heart attacks prevention. Collectively these trials will include more than 65,000 patients at high-risk for cardiovascular and stroke events, and should provide a reliable evidence-base for prevention.
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PMID:Homocysteine, endothelial dysfunction, and coronary artery disease: emerging strategy for secondary prevention. 1263 May 44


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