Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although epidemiological studies suggest that people with minor impairment of renal function are at higher risk of stroke and coronary heart disease, the mechanisms underlying this relation are unclear. One explanation may lie with observations that deterioration in renal function is accompanied by elevations in plasma homocysteine concentrations. There is evidence that moderate hyperhomocysteinemia may play a causal role in atherosclerotic disease. We investigated the relations between renal function, plasma homocysteine and atherosclerosis of the carotid arteries in 128 men and women aged 69-74 years. Renal function was assessed by creatinine clearance and serum creatinine. Duplex ultrasonography was used to quantify the degree of stenosis in the extracranial carotid arteries. Severity of carotid atherosclerosis was greatest in men and women with the poorest renal function, whether measured by creatinine clearance or serum creatinine. After adjustment for plasma homocysteine, pulse pressure and other cardiovascular risk factors, the odds ratio for having carotid stenosis >30% was 4.3 (95% CI 1.4-12.9) in those whose creatinine clearance rate was 55 ml/min or less compared with those whose creatinine clearance rate was >73 ml/min. Even small decrements in renal function were associated with increased risk; people whose creatinine clearance rate was between 56 and 73 ml/min had an odds ratio of 3.8 (95% CI 1.2-11.9). Plasma homocysteine concentrations were significantly higher in people with poorer renal function, but they did not explain the associations we found between carotid atherosclerosis and creatinine clearance or serum creatinine.
 ...
PMID:Renal function, plasma homocysteine and carotid atherosclerosis in elderly people. 1113 93

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.
 ...
PMID:[Hereditary thrombophilia with ischemiC stroke and sinus thrombosis. Diagnosis, therapy and meta-analysis]. 1113 89

During the past year epidemiological studies have linked elevated plasma total homocysteine concentrations with an increased risk of ischaemic stroke because of arterial disease. Laboratory studies have further explored the mitogenic effects of total homocysteine on vascular smooth muscle, and cytotoxic and thrombophilic effects on vascular endothelium. Also, a clinical trial has shown that lowering total homocysteine by means of multivitamin therapy decreases the rate of abnormal exercise electrocardiography tests. However, it remains to be determined whether lowering total homocysteine prevents hard clinical outcome events, such as stroke and other serious vascular events. An alternative explanation for the observed association between elevated total homocysteine and stroke is a confounding effect of factors associated with hyperhomocysteinaemia (e.g. cigarette smoking, renal impairment, an atherogenic diet, cystine deficiency, folate deficiency) or perhaps even the acute vascular events themselves, whereby the tissue damage temporarily increases total homocysteine levels. The results of ongoing clinical trials in stroke patients to determine the impact of multivitamin therapy on recurrent stroke and other serious vascular events are awaited.
 ...
PMID:Homocysteine and stroke. 1117 24

Total blood levels of homocysteine (tHcy) have been shown to depend on both environmental and genetic factors, and to be associated with the risk of developing atherosclerosis with its complications of coronary heart disease (CHD) and stroke. In this study, 408 men and 346 women from two towns, Dewsbury and Maidstone were examined for tHcy levels and genotyped for the C677T and the A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene. Blood tHcy was significantly higher in men from the CHD high risk town of Dewsbury (12.7 micromol/l) than in the low CHD risk town of Maidstone (11.5 micromol/l) P<0.001, but not in women (10.7 vs. 10.5 micromol/l), with women in both towns, thus, showing significantly lower tHcy than men. There was no difference between towns in folate or vitamin B12 levels but the conventional inverse relationship with tHcy was seen. Smoking men and women from both towns had significantly higher tHcy and lower folate levels than non-smoking individuals (P<0.001). The frequency of the 677T allele in Dewsbury was 0.35 (95% CI; 0.32-0.39) compared with 0.29 (95% CI; 0.26-0.32) in Maidstone (P<0.01). Similar frequency difference of borderline statistical significance was seen both for men (P=0.054) and women (P=0.048) in both the towns, suggesting a true regional frequency difference. The effect of the 677T on tHcy was highly significant in the group as a whole with the most profound effect seen in men (12.0 micromol/l for CC vs. 14.1 micromol/l for TT, P<0.001). By contrast, there was no significant effect of the A1298C polymorphism on tHcy, folate or vitamin B12 levels, with no evidence for an interaction with the C677T genotype. The regional differences in tHcy levels were still present after the adjustment for folate and vitamin B12 levels, smoking and the effect of the C677T polymorphism. This suggests that there may be other unidentified factors, either environmental or genetic, affecting tHcy levels, and thus potentially having an impact on the risk of developing hyperhomocysteinaemia and CHD. These observations may have a bearing on regional differences in tHcy levels and the variation in CHD risk between regions in the UK.
 ...
PMID:The effect of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase gene on homocysteine levels in elderly men and women from the British regional heart study. 1125 67

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.
 ...
PMID:Homozygous thermolabile variant of the methylenetetrahydrofolate reductase gene: a potential risk factor for hyperhomocysteinaemia, CVD, and stroke in childhood. 1130 98

Heterozygosity and/or homozygosity for mutations at the genes of the enzymes involved in homocysteine metabolism may confer an increased risk for thrombosis by causing hyperhomocysteinemia. Although the mutations related to homocysteine metabolism possibly increase the risk of stroke, the data are conflicting and there are very few reports linking these defects to acute stroke in children. We aimed to study the role of these mutations in Turkish children with ischemic stroke. Forty-six patients having cerebral infarct were clinically diagnosed, and the infarction verified with magnetic resonance imaging of the brain was included in the study. All patients were below the age of 18 (10 months to 18 years). Sixty-eight controls, consecutively selected among healthy unrelated subjects from the same geographic area of Turkey without personal and family history of thrombosis, stroke or Behest's disease, were included. Genotyping for the common mutations was carried out by the methods described previously. There was no difference between the pediatric stroke patients and controls for the distribution of methylene tetrahydrofolate reductase (MTHFR) 677 C-T, MTHFR 1298 A-C, methylene tetrahydrofolate dehydrogenase (MTHFD) 1958 G-A and methionine synthase reductase (MTRR) 66 A-G alleles. There was no risk for double gene alterations (MTHFR 677 C-T vs. 1298 A-C) after individuals with FV 1691 A mutation is excluded. Twelve of the 46 patients were found to carry FV 1691 A mutation (26.0%), one being homozygote. The cerebral infarct risk for FV 1691 A was found to be 6.4 (CI 95% 1.7-23.0). Eight of the 46 patients were found to carry PT 20210 A mutation (16.6%). Two of the FV 1691 A heterozygous patients carried PT 20210 A mutation at the same time (4.2%). As a conclusion, we can say that FV 1691 A and PT 20210 A mutations are important and must be included to the routine analysis of pediatric stroke patients.
 ...
PMID:Common mutations at the homocysteine metabolism pathway and pediatric stroke. 1132 21

In the past year, evidence from epidemiological studies in patients with renal disease has confirmed associations between both elevated plasma total homocysteine concentrations and the inflammatory marker C-reactive protein with an increased risk of arteriosclerotic vascular disease. However, it remains to be determined whether lowering total homocysteine or reducing inflammation will prevent 'hard' clinical outcome events such as stroke, myocardial infarction, and vascular death. Randomized trials of homocysteine lowering are currently ongoing and should further clarify the nature of the observed association between elevated total homocysteine and cardiovascular risk in patients with or without renal disease, and whether it is causal and modifiable. There are currently no known therapeutic interventions that specifically lower C-reactive protein levels in individuals or the prevalence of elevated C-reactive protein in the population but randomized trials of anti-inflammatory therapy (e.g. using selective cyclo-oxygenase-2 inhibitors) aimed at preventing cardiovascular disease are currently being planned.
 ...
PMID:Associations of homocysteine, C-reactive protein and cardiovascular disease in patients with renal disease. 1134 1

The end-stage renal disease (ESRD) population experiences an excess morbidity and mortality due to arteriosclerotic cardiovascular disease (CVD) outcomes. Specifically, event rates for myocardial infarction and stroke are 5- to 10-fold in ESRD patients on maintenance dialysis than in the general population. Recently, there is controlled evidence that hyperhomocysteinemia occurs more commonly than any of the traditional CVD risk factors in ESRD patients. Prolonged exposure of endothelial cells to homocysteine impairs the production of nitric oxide and endothelium-dependent vasodilatation, they combine with low-density lipoprotein cholesterol to produce aggregates that are taken up by vascular macrophages in the arterial intima (foam cells), produce aggregatory effects on the platelets, and decrease endothelial antithrombotic activity due to changes in the thrombomodulin function. Current treatment regimens for ESRD hyperhomocysteinemia, which are based on the pharmacological doses of folic acid (5 to 15 mg/day), frequently result in suboptimal lowering of Hcy concentrations. Other potential therapeutic approaches (such as oral N-acetylcysteine at 1.2 g/day) merit controlled investigation.
 ...
PMID:Hyperhomocysteinemia in end-stage renal failure. 1137 82

Recent studies have shown that hyperhomocysteinaemia is a common, independent and easily modifiable risk factor for atherosclerotic and thromboembolic diseases such as cerebrovascular disease, coronary artery disease and venous thrombosis. The vascular risk rises continuously across the spectrum of elevated plasma homocysteine concentrations. It is at least as important as cholesterol, lipoprotein abnormalities and hypertension and should be part of risk assessment, especially those at high risk. Moderately elevated plasma homocysteine concentration is readily correctable by folic acid, betaine, or vitamin B12 supplementation. It seems logical to assume that a reduction in homocysteine concentration will reduce the risk of ischaemic stroke, but there are as yet no published data to prove this. This review will discuss the aetiology and possible treatment of hyperhomocysteinaemia causing ischaemic stroke.
 ...
PMID:Aetiology and treatment of hyperhomocysteinaemia causing ischaemic stroke. 1140 12

Higher levels of plasma homocysteine are associated with a variety of atherosclerotic conditions that are particularly pertinent to elderly persons. Cross sectional data have suggested that the lower deciles of plasma and dietary folate are highly associated with the presence of carotid stenosis in the elderly. Recent prospective studies have demonstrated strong associations between elevated concentrations of homocysteine and the incidence of cardiovascular mortality, total mortality, and stroke in elderly men and women. The impact of folate fortification on homocysteine levels has been assessed in middle-aged adults, but the clinical impact of fortification or supplementation of the diet with folate on clinical end points of cardiovascular disease is presently unknown, although clinical trials with folate supplementation are underway. (c) 2000 by CVRR, Inc.
 ...
PMID:CME Paper: Homocysteine: The New Risk Factor for Cardiovascular Disease in the Elderly. 1141 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>