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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe homocystinemia is frequently associated with vascular disease while the pathological consequences of moderate or slightly elevated plasma homocysteine are unknown. Cobalamin and folate deficiencies may result in an elevation of plasma homocysteine. A sensitive and reproducible assay for total plasma homocysteine has been developed. The essential steps in the assay include (i) conversion of homocysteine disulfides to free homocysteine with borohydride reduction; (ii) conjugation of homocysteine with monobromobimane; (iii) separation of homocysteine-bimane from other plasma thiol-bimane adducts by reverse-phase high-performance liquid chromatography; and (iv) detection and quantitation of homocysteine-bimane by fluorometry. The method has a sensitivity of 4.4 pmol of homocysteine and is highly reproducible (intra- and interassay coefficients of variation = 4.97 and 4.53%, respectively). The mean concentration of total plasma homocysteine in nonfasting adult males (n = 12) and females (n = 12) was 15.8 (range, 7.0-23.7) and 16.5 nmol/ml (range, 8.6-20.7), respectively. Markedly elevated levels of homocysteine were found in patients with cobalamin and folate deficiency. Total plasma homocysteine represents approximately 4% of borohydride-generated thiol reactivity in the plasma of normal individuals.
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PMID:Determination of plasma homocysteine by high-performance liquid chromatography with fluorescence detection. 272 75

Elevated plasma homocyst(e)ine levels are an independent risk factor for vascular disease. In a case-control study, the authors studied the associations of fasting plasma homocyst(e)ine and vitamins, which are important cofactors in homocysteine metabolism, with the risk of myocardial infarction. The cases were 130 Boston area patients hospitalized with a first myocardial infarction and 118 population controls, less than 76 years of age, enrolled in 1982 and 1983. Dietary intakes of vitamins B6, B12, and folate were estimated from a food frequency questionnaire. After adjusting for sex and age, the authors found that the geometric mean plasma homocyst(e)ine level was 11% higher in cases compared with controls (p = 0.006). There was no clear excess of cases with extremely elevated levels. The age- and sex-adjusted odds ratio for each 3-mumol/liter (approximately 1 standard deviation) increase in plasma homocyst(e)ine was 1.35 (95% confidence interval 1.05-1.75; p trend = 0/007). After further control for several risk factors, the odds ratio was not affected, but the confidence interval was wider and the p value for trend was less significant. Dietary and plasma levels of vitamin B6 and folate were lower in cases than in controls, and these vitamins were inversely associated with the risk of myocardial infarction, independently of other potential risk factors. Vitamin B12 showed no clear association with myocardial infarction, although methylmalonic acid levels were significantly higher in cases. Comparing the mean levels of several homocysteine metabolites among cases and controls, the authors found that impairment of remethylation of homocyst(e)ine (dependent of folate and vitamin B12 rather than on vitamin B6-dependent transsulfuration) was the predominant cause of high homocyst(e)ine levels in cases. Accordingly, plasma folate and, to a lesser extent, plasma vitamin B12, but not vitamin B6, correlated inversely with plasma homocyst(e)ine, even for concentrations at the high end of normal values. These data provide further evidence that plasma homocyst(e)ine is an independent risk factor for myocardial infarction. In this population, folate was the most important determinant of plasma homocyst(e)ine, even in subjects with apparently adequate nutritional status of this vitamin.
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PMID:Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate. 861 Jun 98

Diabetic patients have increased morbidity and mortality attributable to myocardial infarction, cerebrovascular disease and peripheral vascular disease, due to a high incidence of premature atherosclerosis. Abnormalities of hemostasis have been reported in many studies on diabetes over almost thirty years, but unfortunately the results have often appeared contradictory. The hemostatic alterations could lead to increased risk of vascular disease in diabetic patients. We have studied some coagulation factors (Fibrinogen, Factor II, Factor VII) and coagulation inhibitors (Protein C, Protein S), and plasminogen in fifty-four type 2 diabetic patients. The possible relationship between coagulation factors and coagulation inhibitors and parameters for glyco-metabolic control (glycosylated hemoglobin, fructosamine) and disturbed lipid metabolism (cholesterol, triglycerides) have ben analyzed. Our results show increase of fibrinogen, correlated with the metabolic control of the disease, positive correlation between plasminogen, factor II, protein S and hypertriglycerides, decreased levels of protein C correlated neither with metabolic control of disease neither with disturbed lipid metabolism.
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PMID:[Evaluation of the coagulation and fibrinolysis system in 54 patients with type 2 diabetes mellitus: correlations with lipid metabolism and blood glucose control]. 876 54

Mild to moderate homocysteinemia in women has been associated with an increased frequency of pregnancies with neural tube defects (NTD). Homocysteinemia is also an independent risk factor for premature vascular disease. In addition to folic acid, supplemental Vitamin B12, Vitamin B6 and betaine may normalize homocysteine metabolism, decrease the risk for NTD formation, and correct related metabolic imbalances in children with NTD. By means of automated amino acid analysis, we assessed total non-fasting homocysteine and methionine in plasma from 24 children with myelomeningocele. This study group (mean age 10.5 +/- 4.9 years) included 12 girls and 12 boys randomly selected from our Birth Defects Clinic. Homocysteine concentrations in our patients (4.7 +/- 1.8 mumol/L) did not differ from those of 20 randomly selected child controls (5.1 +/- 2.6 mumol/L). The mean homocysteine concentration for 36 adult controls (9.3 +/- 3.0 mumol/L) was significantly higher than the mean for either group of children (p < 0.0001). Linear regression analysis revealed negative correlation of total plasma homocysteine with serum folate (r = -0.53; p = 0.01), but not of homocysteine with either methionine or B12. Plasma methionine concentrations from our patients did not differ from adult reference values. Elevated homocysteine in some mothers of children with NTD has been attributed to defective methylation of homocysteine. These preliminary results do not indicate such a defect in the children themselves. A more comprehensive study of homocysteine, methionine and related metabolites in children with NTD and age-matched controls will be required to determine the clinical significance of these findings.
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PMID:Plasma homocysteine and methionine concentrations in children with neural tube defects. 900 10

Epidemiological studies have shown that higher blood homocysteine levels appear to be associated with higher risks of coronary, cerebral, and peripheral vascular disease and are inversely related to blood levels of folate and of vitamin B12 and vitamin B6. However, observational studies cannot exclude the possibility that elevated homocysteine levels may be associated with some other factor, rather than being causally related to vascular disease. Large-scale clinical trials of sufficient dose and duration of treatment are required to test this hypothesis, but there was substantial uncertainty about the optimal vitamin regimen to test in such trials. A meta-analysis of 12 randomized trials of vitamin supplements to lower homocysteine levels was carried out to determine the optimal dose of folic acid required to lower homocysteine levels and to assess whether vitamin B12 or vitamin B6 had additive effects. This meta-analysis demonstrated that reductions in blood homocysteine levels were greater at higher pretreatment blood homocysteine levels and at lower pretreatment folate concentrations. After standardization for a pretreatment homocysteine concentration of 12 micromol/L and folate concentration of 12 nmol/L (approximate average concentrations for western populations), dietary folic acid reduced homocysteine levels by 25% (95% confidence interval [CI]: 23 to 28%) with similar effects in a daily dosage range of 0.5 to 5 mg. Vitamin B12 (mean 0.5 mg) produced an additional reduction in blood homocysteine of 7%, whereas vitamin B6 (mean 16.5 mg) did not have any significant effect. Hence, in typical populations, daily supplementation with both 0.5 to 5 mg folic acid and about 0.5 mg vitamin B12 would be expected to reduce homocysteine levels by one quarter to one third (from about 12 micromol/L to about 8 to 9 micromol/L). Large-scale randomized trials of such regimens are now required to determine whether lowering homocysteine levels by folic acid and vitamin B12, with or without added vitamin B6, reduces the risk of vascular disease.
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PMID:Vitamin supplements and cardiovascular risk: review of the randomized trials of homocysteine-lowering vitamin supplements. 1101 52

The objective of this study was to determine the size of reduction in homocysteine concentrations produced by dietary supplementation with folic acid and with vitamins B12 or B6. Meta-analysis of individual data on 1114 people in 12 randomised controlled trials assessed the effects of folic acid-based supplements on blood homocysteine concentrations. Multivariate regression analysis was used to determine the effects on homocysteine concentration of different doses of folic acid and of the addition of vitamin B12 or B6. The results showed that the proportional and absolute reductions in blood homocysteine produced by folic acid supplements were greater at higher pre-treatment blood homocysteine concentrations (p<0.001) and at lower pre-treatment blood folate concentrations (p<0.001). After standardisation to pre-treatment blood concentrations of homocysteine of 12 micromol/L and of folate of 12 nmol/L (approximate average concentrations for Western populations), dietary folic acid reduced blood homocysteine concentrations by 25 percent (95% confidence interval 23%-28%; p<0.001), with similar effects in the range of 0.5-5 mg folic acid daily. Vitamin B12 (mean 0.5 mg daily) produced an additional 7 percent (3%-10%) reduction in blood homocysteine. Vitamin B6 (mean 16.5 mg daily) did not have a significant additional effect. In conclusion, typically in Western populations, daily supplementation with both 0.5-5 mg folic acid and about 0.5 mg vitamin B12 would be expected to reduce blood homocysteine concentrations by about a quarter to a third (for example, from about 12 micromol/L to 8-9 micromol/L). Large scale randomised trials of such regimens in high risk populations are now needed to determine whether lowering blood homocysteine concentration reduces the risk of vascular disease.
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PMID:Lowering blood homocysteine with folic acid-based supplements: meta-analysis of randomised trials. 1133 43

Hyperhomocysteinemia, a risk factor for vascular disease, is commonly found in adult patients with end-stage renal disease. Major determinants of elevated plasma homocysteine levels in these patients include deficiencies in folate and vitamin B12, methylenetetrahydrofolate reductase (MTHFR) genotype and renal function. Little information is available for children with chronic renal failure (CRF). The prevalence and the factors that affect plasma homocysteine concentration were determined in children. Twenty-nine children with various degrees of CRF (15 were dialyzed, 14 were not dialyzed) were compared with 57 age- and sex-matched healthy children. Homocysteine concentrations were higher in patients than controls (17.3 micromol/l vs 6.8 micromol/l, P<0.0001) and hyperhomocysteinemia (>95th percentile for controls: 14.0 micromol/l) was seen in 62.0% of patients and 5.2% of controls. Folate concentrations were lower in patients (9.9 nmol/l) than controls (13.5 nmol/l), P<0.01. Vitamin B12 was similar in patients (322 pmol/l) and controls (284 pmol/l). Dialyzed patients have a higher prevalence of hyperhomocysteinemia than nondialyzed patients (87% vs 35%). Dialyzed patients with MTHFR mutation have higher plasma homocysteine (28.5 micromol/l) than nondialyzed patients with the mutation (10.7 micromol/l), P<0.002. In our study, differences between controls and patients in plasma homocysteine concentrations are observed when age is greater then 92 months, folate less than 21.6 nmol/l and vitamin B12 less than 522 pmol/l. Our study shows that hyperhomocysteinemia is common in children with CRF and is associated with low folate and normal vitamin B12 status, compared to normal children. Among the patients, the dialyzed patients with the MTHFR mutation are particularly at risk for hyperhomocysteinemia. Further studies are needed to investigate therapeutic interventions and the potential link with vascular complications in these patients.
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PMID:Plasma homocysteine concentration in children with chronic renal failure. 1160 87

Hyperhomocysteinemia, a risk factor for vascular disease, may be a particular problem in Asian Indians, but information is limited, especially in the U.S., despite its growing Asian population. Moreover, suggestions have been made that folate deficiency is responsible for the hyperhomocysteinemia in Indians. Therefore, we studied homocysteine status in healthy Asian Indians in the U.S. prospectively, determined the frequency of cobalamin and folate deficiency as contributors to it, and examined whether food-cobalamin absorption contributed to cobalamin deficiency. Homocysteine levels were higher in Asian Indian men than in 4 other ethnic groups (P < 0.0001); 10/39 Indian men (25.6%) were hyperhomocysteinemic. Cobalamin levels were lower in Indian men (P = 0.000005) and women (P = 0.03) than in non-Indians; low levels were found more frequently in both Indian men (23/39; 59.0%) and women (5/21; 23.8%) than in others. Measuring methylmalonic acid in 10 selected subjects showed that the low cobalamin levels reflected cobalamin deficiency, and high methylmalonic acid levels were found in some subjects without hyperhomocysteinemia. Evidence of folate deficiency was not found in any subjects. Food-cobalamin absorption was normal in all 13 Indian subjects tested, including those with Helicobacter pylori infection. The results show that hyperhomocysteinemia is strikingly common in apparently healthy, young Asian Indian men. The cause appears to be cobalamin deficiency, which affected more than half of the Indian men, may be largely subclinical, is underestimated by homocysteine levels alone which were not always abnormal, and is probably largely dietary in origin. Folate deficiency is rare. This public health problem is amenable to prevention and treatment in this growing segment of the U.S. population. It was, parenthetically, noteworthy that many of the affected subjects were young physician trainees.
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PMID:Hyperhomocysteinemia and cobalamin deficiency in young Asian Indians in the United States. 1255 23

Vascular disease and its risk factors have been associated with the age-related hearing loss. We examined the association of elevated plasma homocysteine and its determinants with hearing levels. Pure-tone air conduction thresholds in 728 individuals with sensorineural hearing loss were not associated with homocysteine, erythrocyte folate and Vitamin B6. Low concentrations of serum folate and Vitamin B12 were associated with better hearing. When folate status was below the median, 5,10-methylenetetrahydrofolate reductase (MTHFR) 677TT homozygotes had similar hearing levels to subjects with a C allele. However, when folate status was above the median, MTHFR 677TT homozygotes had on an average 5 dB (p = 0.037) and 2.6 dB (p = 0.021) lower PTA-high and PTA-low hearing thresholds, respectively, than the subjects with a 677C allele. The relationship between serum folate and hearing thresholds appeared to be dependent on MTHFR 677 genotype (CC, r = 0.13, p = 0.034; TT, r = -0.10, p = 0.291). This supports the hypothesis that a greater one-carbon moiety commitment to de novo synthesis of nucleotides and an increase in formyl-folate derivatives relative to methyl-folate derivatives is protective for hearing.
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PMID:Association of folate with hearing is dependent on the 5,10-methylenetetrahdyrofolate reductase 677C-->T mutation. 1646 57

The aim of the present study was to examine the effects of raloxifene (RLX) and tibolone (TBN) on plasma homocysteine (Hcy) levels and their relationship with atherosclerotic changes in the walls of the carotid artery in ovariectomised rats. Thirty surgically ovariectomised Wistar albino rats after a menopausal period of 6 cycles were randomly assigned to receive RLX 0.01 mg/kg/day (n=10), TBN 0.04 mg/kg/day (n=10) and the same dose of placebo (n=10) for 6 cycles. Serum levels of vitamin B12, folate and Hcy were measured and carotid arteries were examined histopathologically following the termination of treatment. Hcy levels were 3.27+/-0.97, 2.57+/-0.32 and 2.28+/-0.12 micromol/l, Vitamin B12 levels were 901.90+/-239.76, 694.70+/-112.20 and 631+/-309.44 pg/ml and folate levels were 73.80+/-12.71, 72.51+/-7.05 and 84.79+/-20.82 ng/ml in receiving RLX, TBN and placebo respectively. Hcy levels were increased by RLX vs. placebo (P=0.006) but not by TBN vs. placebo (P=0.070). Vitamin B12 levels were found to be elevated by TBN vs. the control group (P=0.041) but not by RLX vs. placebo (P=0.059). Histopathological examination of carotid arteries from rats receiving both RLX and TBN revealed no difference vs. placebo. Data obtained from the study support the view that neither RLX nor TBN appears to have a primary protective effect on vascular disease by effecting the metabolism of Hcy at menopause.
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PMID:The effects of raloxifene and tibolone on homocysteine and vascular histopathological changes. 1818 27


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