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

Moderate hyperhomocysteinaemia is a frequent finding in atherothrombotic cerebrovascular disease. This study confirms and extends this observation. Hyperhomocysteinaemia was present in 57 of 142 survivors with stroke (40%) and in four of 66 controls (6%). Plasma homocysteine concentrations were increased not only in carotid artery disease or lucunar stroke but also in haemorrhagic or embolic strokes. Homocysteine values were unrelated to the presence of hypertension, smoking, or hypercholesterolaemia, or to the concentrations of blood glucose, glycosylated haemoglobin, and plasma fibrinogen. Multiple regression analysis of the patient data showed that about 40% of the variation in plasma homocysteine concentrations could be predicted by the values for the homocysteine metabolism cofactors, blood folate and plasma pyridoxal 5-phosphate and by renal function as reflected in the values for serum creatinine. In patients, urine excretion of homocysteine per unit creatinine was significantly increased and strongly correlated both to the plasma homocysteine concentration and to the values for blood folate, plasma pyridoxal 5-phosphate, and serum vitamin B12. We conclude that moderate hyperhomocysteinaemia is frequently present in cases of stroke, is independent of other stroke risk factors or the type of stroke, and is partly related to renal function and the concentrations of homocysteine metabolism cofactors.
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PMID:Hyperhomocysteinaemia in stroke: prevalence, cause, and relationships to type of stroke and stroke risk factors. 158 47

A significantly higher concentration of plasma homocysteine compared with controls was noted in a group of alcoholics (n = 42) hospitalized for detoxication. Normal concentrations of plasma homocysteine were reached within 1 or 2 weeks after admission to the hospital. In another group of abstinent alcoholics (n = 16) plasma homocysteine did not deviate from that of controls. Since hyperhomocysteinemia has been associated with premature vascular disease, we speculate that the increased plasma homocysteine in alcoholics might cause the increased incidence of stroke found in these patients.
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PMID:Elevated plasma homocysteine in alcoholics. 839 19

Mild hyperhomocysteinemia, due to genetic or to environmental factors, is now recognized as a risk factor for premature arterial disease, including peripheral arterial occlusion, thrombotic stroke and myocardial infarction. It is defined by either an increased level of fasting homocysteine or by an increased level after loading with methionine, which is more frequently altered than the former. We studied the hemostatic parameters in 88 patients with premature arterial disease (mean age 43 +/- 11 years). We confirmed previously known hemostatic alterations described in vascular patients when compared to controls, but found that, among patients, some of these parameters were more altered in hyperhomocysteinemic patients. When fasting homocysteine was increased, higher alterations were found in factors VIIIc, von Willebrand and thombin-antithrombin complexes were more elevated. When post-methionine load homocysteine was increased, alterations in fibrinolytic parameters were more pronounced.
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PMID:Mild hyperhomocysteinemia and hemostatic factors in patients with arterial vascular diseases. 906 95

Severely elevated levels of total homocysteine (approximately millimolar) in the blood typify the childhood disease homocystinuria, whereas modest levels (tens of micromolar) are commonly found in adults who are at increased risk for vascular disease and stroke. Activation of the coagulation system and adverse effects of homocysteine on the endothelium and vessel wall are believed to underlie disease pathogenesis. Here we show that homocysteine acts as an agonist at the glutamate binding site of the N-methyl-D-aspartate receptor, but also as a partial antagonist of the glycine coagonist site. With physiological levels of glycine, neurotoxic concentrations of homocysteine are on the order of millimolar. However, under pathological conditions in which glycine levels in the nervous system are elevated, such as stroke and head trauma, homocysteine's neurotoxic (agonist) attributes at 10-100 microM levels outweigh its neuroprotective (antagonist) activity. Under these conditions neuronal damage derives from excessive Ca2+ influx and reactive oxygen generation. Accordingly, homocysteine neurotoxicity through overstimulation of N-methyl-D-aspartate receptors may contribute to the pathogenesis of both homocystinuria and modest hyperhomocysteinemia.
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PMID:Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. 915 76

Hyperhomocysteinemia is a condition which, in the absence of kidney disease, indicates a disrupted sulfur amino acid metabolism, either because of vitamin (folate, B12 and B6) deficiency or a genetic defect. Epidemiological evidence suggests that mild hyperhomocysteinemia is associated with increased risk of arteriosclerotic disease and stroke. The relationship between hyperhomocysteinemia and thrombosis has been investigated in 10 studies involving a total of 1200 patients and 1200 controls. Eight of these studies demonstrated positive association with odds ratios that ranged from 2 to 13. This association was enhanced by including a methionine loading test. There is some evidence which suggests that hyperhomocysteinemia and APC resistance have a synergistic effect on the onset of thrombotic disease. Studies on the mechanism that underlies the relationship between thrombosis and hyperhomocysteinemia used non-physiologically high levels of homocysteine, rendering the data doubtful as to their patho-physiological relevance.
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PMID:Hyperhomocysteinemia and thrombosis: acquired conditions. 919 9

Homocysteine is a graded risk factor for the incidence of stroke and for the degree of carotid atherosclerosis. Homocysteine is also a graded risk factor for the incidence of myocardial infarction but we do not know its precise relations to the severity of atherosclerosis in coronary patients. Seventy five symptomatic coronary patients were recruited for the study. Fifty of these patients had coronary artery disease only and were compared in a case-control manner to 50 healthy controls matched for age and sex. The 25 other coronary patients had also symptoms in another atherosclerotic territory (cerebral, peripheral or both) and were also compared to 25 matched controls. Mean plasma homocysteine level was significantly higher in coronary patients than in controls (11.7 +/- 0.7 mumol l-1, n = 50 versus 9.9 +/- 0.5 mumol l-1, n = 50, p < 0.05). Homocysteine in patients with symptomatic atherosclerosis in two or three arterial sites was 15.7 +/- 1.5 mumol l-1 which differed significantly from matched controls and from patients with coronary artery disease only (p = 0.01). The extent of coronary atherosclerosis evaluated by an angiographic coronary score correlated weakly to plasma homocysteine levels (r = 0.25, p < 0.05). The patients with both hypertension and high levels of homocysteine (> 11.3 mumol l-1, median value) had more severe coronary atherosclerosis (coronary score of 16.3 +/- 2.3 versus 11.9 +/- 0.9, p < 0.05) and more diffuse atherosclerosis (number of atherosclerotic territories of 1.5 +/- 0.2 versus 1.2 +/- 0.7, p = 0.08) than the coronary patients without this association. There were no other high risk association when considering the other classical risk factors. Thus, the highest levels of homocysteine were present in patients with coronary disease and another symptomatic localisation of atherosclerosis. A small gradient in the extent of coronary atherosclerosis was found with increasing levels of homocysteine. The presence of both hypertension and hyperhomocysteinemia was associated with more severe coronary atherosclerosis.
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PMID:Plasma homocysteine and the extent of atherosclerosis in patients with coronary artery disease. 926 41

Although hyperhomocysteinemia has been recognized recently as a prevalent risk factor for myocardial infarction and stroke, the mechanisms by which it accelerates arteriosclerosis have not been elucidated, mostly because the biological effects of homocysteine can only be demonstrated at very high concentrations and can be mimicked by cysteine, which indicates a lack of specificity. We found that 10-50 microM of homocysteine (a range that overlaps levels observed clinically) but not cysteine inhibited DNA synthesis in vascular endothelial cells (VEC) and arrested their growth at the G1 phase of the cell cycle. Homocysteine in this same range had no effect on the growth of vascular smooth muscle cells (VSMC) or fibroblasts. Homocysteine decreased carboxyl methylation of p21(ras) (a G1 regulator whose activity is regulated by prenylation and methylation in addition to GTP-GDP exchange) by 50% in VEC but not VSMC, a difference that may be explained by the ability of homocysteine to dramatically increase levels of S-adenosylhomocysteine, a potent inhibitor of methyltransferase, in VEC but not VSMC. Moreover, homocysteine-induced hypomethylation in VEC was associated with a 66% reduction in membrane-associated p21(ras) and a 67% reduction in extracellular signal-regulated kinase 1/2, which is a member of the mitogen-activated protein (MAP) kinase family. Because the MAP kinases have been implicated in cell growth, the p21(ras)-MAP kinase pathway may represent one of the mechanisms that mediates homocysteine's effect on VEC growth. VEC damage is a hallmark of arteriosclerosis. Homocysteine-induced inhibition of VEC growth may play an important role in this disease process.
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PMID:Inhibition of growth and p21ras methylation in vascular endothelial cells by homocysteine but not cysteine. 931 59

Hyperhomocysteinemia is regarded as a risk factor for stroke but its pathogenetic role has not yet been established in Black patients. We studied 24 Black patients admitted with cerebral thrombosis, and compared them with age- and sex-matched apparently healthy controls from the same community. Total homocysteine (tHcy) (free homocysteine, protein-bound homocysteine, the disulfide homocystine and the mixed disulfide homocysteine-cysteine) concentration was 10.91 (4.95-23.05) mumol/l in the stroke patients and 8.73 (3.95-15.10) mumol/l in controls (p = 0.031). This difference could not be explained by differences in vitamin B12, vitamin B6 or folate status. A subgroup of nine stroke patients with hypercreatininaemia (> 90 mumol/l, 75% of control concentrations) had significantly higher plasma tHcy concentrations [median (range) 9.10 (5.40-15.10) mumol/l] compared with controls [8.65 (3.96-13.89) mumol/l] (p = 0.002). Plasma tHcy concentrations of stroke patients with normal serum creatinine concentrations were not significantly different to those of controls. Hyperhomocysteinemia in Black patients with stroke may be partially caused by renal insufficiency. Therefore, while hyperhomocysteinemia may increase the risk of stroke, it is unlikely to be a primary initiating factor.
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PMID:Hyperhomocysteinaemia in black patients with cerebral thrombosis. 941 45

A case is presented of a woman who had an occlusive stroke at age 29. She was seen in a rehabilitation medicine clinic for central nervous system-mediated pain that had developed soon after a cerebrovascular event. After an extensive workup to find the cause of her cerebrovascular occlusion, it was discovered that she had a markedly elevated fasting plasma homocysteine level of 59 micromol/L. A discussion of premature vascular disease in the rehabilitation patient is followed by a short review of the clinical detection of, and potential therapy for, hyperhomocysteinemia.
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PMID:Hyperhomocysteinemia as a cause of premature stroke in a young patient. 952 90

Hyperhomocysteinemia is a condition which, in the absence of kidney disease, indicates a disrupted sulfur amino acid metabolism, either because of vitamin deficiency (folate, B12 and B6) or a genetic defect. Epidemiologic evidence suggests that mild hyperhomocysteinemia is associated with increased risk of arteriosclerotic disease and stroke. The relationship between hyperhomocysteinemia and thrombosis has been investigated in 10 studies involving a total of 1200 patients and 1200 controls. Eight of these studies demonstrated positive association with odds ratios that ranged from two to 13. This association was enhanced by including a methionine loading test. There is some evidence which suggests that hyperhomocysteinemia and activated protein C resistance have synergistic effect on the onset of thrombotic disease. Recent studies with animal models for mild hyperhomocysteinemia provided encouraging results in the understanding of the mechanism that underlies this relationship between mild elevations of plasma homocysteine and vascular disease. These animal models pointed to the possibility that the effect of elevated homocysteine is multifactorial, affecting both the vascular wall structure and the blood coagulation system.
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PMID:Relationship between homocysteine and thrombotic disease. 970 66


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