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

Homocystinuria is a rare inherited metabolic disease. Arterial and venous thromboembolic events represent frequent and life-threatening complications in homocystinuric patients. It has been suggested that mild homocysteinemia could be a risk factor for vascular disease. We have therefore measured total plasma homocysteine (HCy) concentrations by radioisotopic assay in 50 subjects with venous or arterial thrombosis and studied the relationship between HCy, coagulation and fibrinolytic parameters. Values were considered abnormal if they were higher than 2.7 standard deviations (SD) above the mean, i.e., 14.1 mmol/l. Thus, eighteen of the 50 patients with thrombosis were classified in the hyperhomocysteinemia group. Nine of these subjects had only this isolated risk factor. No correlations were found between HCy and antithrombin III, protein C, protein S and plasminogen levels, or plasma plasminogen activator inhibitor activity. Nevertheless, the correlation between tissue-plasminogen activator antigen and total plasma HCy was significant (r = 0.61, p < 0.001). Increased homocysteinemia seems to be a risk factor for thrombotic events especially knowing that HCy presents a direct cytotoxic effect. Vitamin therapy, already used in homozygote homocystinuric patients, might be beneficial in the prevention of thromboembolic disease in heterozygous patients.
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PMID:Elevated total plasma homocysteine, a risk factor for thrombosis. Relation to coagulation and fibrinolytic parameters. 832 83

Mild homocysteinemia occurs surprisingly often in patients with premature vascular disease. We studied the possible enzymatic sources of this mild hyperhomocysteinemia and the control of homocysteine levels in plasma by treatment of patients with the cofactors and cosubstrates of homocysteine catabolism. We assessed homocysteine metabolism in 131 patients who had premature disease in their coronary, peripheral, or cerebrovascular circulation by using a standard oral methionine-load test. Impaired homocysteine metabolism occurred in 28 patients. We assayed levels of the primary enzymes of homocysteine catabolism in cultured skin fibroblast extracts from 15 of these 28 patients. The patients' cystathionine beta-synthase levels (3.68 +/- 2.52 nmol/h per milligram of cell protein, mean +/- SD) were markedly depressed compared with those from 31 healthy adult control subjects (7.61 +/- 4.49, P < .001). The patients' levels of 5-methyltetrahydrofolate: homocysteine methyltransferase were normal. While betaine: homocysteine methyltransferase was not expressed in skin fibroblasts, 24-hour urinary betaine and N,N-dimethylglycine measurements were consistent with normal or enhanced remethylation of homocysteine by betaine: homocysteine methyltransferase in the 13 patients tested. When treated daily with choline and betaine, pyridoxine, or folic acid, there was a normalization of the postmethionine plasma homocysteine level in 16 of 19 patients. Our results indicate that mild homocysteinemia in premature vascular disease may be caused by either a folate deficiency or deficiencies in cystathionine beta-synthase activity. It does not necessarily involve deficiencies of either 5-methyltetrahydrofolate:homocysteine methyltransferase or betaine:homocysteine methyltransferase. Effective treatment regimens are also defined.
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PMID:Disordered methionine/homocysteine metabolism in premature vascular disease. Its occurrence, cofactor therapy, and enzymology. 836 9

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

We measured the vitamin B-6, vitamin B-12, and folic acid nutritional status in a group of apparently healthy men (n = 44) with moderate hyperhomocysteinemia (plasma homocysteine concentration > 16.3 mumol/L). Compared with control subjects (n = 274) with normal plasma homocysteine (< or = 16.3 mumol/L) concentrations, significantly lower plasma concentrations of pyridoxal-5'-phosphate (P < 0.001), cobalamin (P < 0.001), and folic acid (P = 0.004) were demonstrated in hyperhomocysteinemic men. The prevalence of suboptimal vitamin B-6, B-12, and folate status in men with hyperhomocysteinemia was 25.0%, 56.8%, and 59.1%, respectively. In a placebo-controlled follow-up study, a daily vitamin supplement (10 mg pyridoxal, 1.0 mg folic acid, 0.4 mg cyanocobalamin) normalized elevated plasma homocysteine concentrations within 6 wk. Because hyperhomocysteinemia is implicated as a risk factor for premature occlusive vascular disease, appropriate vitamin therapy may be both efficient and cost-effective to control elevated plasma homocysteine concentrations.
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PMID:Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia. 841 64

In the setting of an outpatient diabetic clinic, we determined whether macrovascular disease in patients with diabetes mellitus is associated with hyperhomocysteinemia (elevated plasma homocysteine [H(e)] concentrations) following a methionine load. Methionine-load tests were performed in 18 healthy controls, 11 diabetics without vascular disease (five insulin-dependent [IDDM] and six non-insulin-dependent [NIDDM]); and 17 diabetics with vascular disease (five IDDM and 12 NIDDM). All subjects were male, and there was no significant difference in mean age among the three groups. We measured plasma H(e) concentrations before and 2, 4, 6, 8, and 24 hours after an oral methionine load. Hyperhomocysteinemia (peak plasma H(e) concentration > control mean +/- 2 SD) occurred with significantly greater frequency (seven of 18, 39%) in patients with NIDDM as compared with age-matched controls (7%), being more common in those with macrovascular disease (five of 12, 41%). The area under the curve (AUC) over 24 hours, reflecting the total period of exposure to H(e), was also elevated with greater frequency in patients with NIDDM and macrovascular disease (33%) as compared with controls (0%). We conclude that hyperhomocysteinemia is associated with macrovascular disease in a significant proportion of patients with NIDDM. Further investigation of this association may determine whether hyperhomocysteinemia contributes to the increased frequency and accelerated clinical course of vascular disease in patients with diabetes mellitus.
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PMID:Hyperhomocysteinemia following a methionine load in patients with non-insulin-dependent diabetes mellitus and macrovascular disease. 854 71

The link between vascular disease and elevated homocysteine levels has been recognized for more than 30 years, and an association with moderately elevated levels has been suspected for 20 years. The initial investigations were case series, cross-sectional, and case-control studies. Those studies consistently suggest a strong positive relationship between moderate hyperhomocysteinemia and risk of vascular disease. However, a major limitation of these types of study design is that the possibility of elevated homocysteine levels being influenced by the disease or its treatment cannot be ruled out. In case-control studies there is always concern about the appropriateness of the control group. These issues pose much less of a problem in prospective designs. Prospective studies also offer the opportunity to study various manifestations of cardiovascular disease at the same time. However, prospective studies tend to be more expensive and time-consuming, perhaps explaining the smaller number of prospective studies and why the first was not published until 1992. The distinct limitations and advantages of prospective studies are also reviewed.
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PMID:Prospective studies of homocysteine and cardiovascular disease. 858 86

Mild elevation of plasma homocysteine is an independent risk factor for vascular disease. We studied the role of 5-methyltetrahydrofolate (5-MTHF), the folate form directly involved in homocysteine metabolism, in contrast to previous studies, which used total folate measurements, in 70 coronary artery disease (CAD) patients and control subjects. We also measured S-adenosylmethionine (SAM), which controls the activity of critical enzymes of homocysteine metabolism. Fasting plasma total homocysteine was elevated (> 12.4 mumol/L for women, > 13.3 mumol/L for men) in 17% of patients, in accordance with earlier studies. These patients showed lower 5-MTHF (12.4 +/- 1.0 mumol/L, mean +/- SD) than control subjects (24.2 +/- 15.0, P < .001), and there was a clear correlation (multiple linear regression analysis: P = .002) of this relevant form of folate with homocysteine. However, 37% of the normohomocysteinemic patients also revealed similarly low 5-MTHF levels, suggesting that a decrease of 5-MTHF does not necessarily cause hyperhomocysteinemia. SAM was significantly decreased in patients (1.4 +/- 0.4 mumol/L) compared with control subjects (1.8 +/- 0.3, P < .001) but was not correlated to homocysteine or 5-MTHF. The correlation between homocysteine and 5-MTHF that was found in CAD patients but not in control subjects confirms the direct relationship between these compounds in vivo. The new finding of low SAM in patients demands further studies, since it might indicate that low levels pose risk and that SAM might be a protective factor against the development of CAD.
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PMID:Low whole-blood S-adenosylmethionine and correlation between 5-methyltetrahydrofolate and homocysteine in coronary artery disease. 864 Mar 99

Recent studies demonstrated associations between occlusive vascular disease and hyperhomocysteinemia of both genetic and nutritional origin. In the present study we analyzed plasma samples from the 20th biannual examination of the Framingham Heart Study cohort to determine distribution of plasma homocysteine concentrations with emphasis on relationships to B vitamins and prevalence of carotid artery stenosis. Results showed that homocysteine exhibited strong inverse association with plasma folate and weaker associations with plasma vitamin B-12 and pyridoxal-5'-phosphate (PLP). Homocysteine was also inversely associated with intakes of folate and vitamin B-6, but not vitamin B-12. Prevalence of high homocysteine (>14 micromol/l) was 29.3% in this cohort, and inadequate plasma concentrations of one or more B vitamins appear to contribute to 67% of the cases of high homocysteine. Prevalence of stenosis > or = 25% was 43% in men and 34% in women with an odds ratio of 2.0 for individuals in the highest homocysteine quartile (> or = 14.4 micromol/l) compared with those in the lowest quartile (< or = 9.1 micromol/l), after adjustment for sex, age, high density lipoprotein cholesterol, systolic blood pressure and cigarette smoking (Ptrend < 0.001). Plasma concentrations of folate and pyridoxal-5'-phosphate and folate intake were inversely associated with extracranial carotid stenosis after adjustment for age, sex and other risk factors.
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PMID:Relationship between plasma homocysteine, vitamin status and extracranial carotid-artery stenosis in the Framingham Study population. 864 67

Reduced, oxidized and protein-bound forms of homocysteine (Hcy), cysteine and cysteinylglycine in plasma interact via redox and disulphide exchange reactions, and these aminothiol species comprise a dynamic system referred to as redox thiol status. Notably, in plasma reduced cysteine is the most abundant low molecular weight sulfhydryl compound. Elevation of plasma Hcy (hyperhomocysteinemia) causes changes in redox thiol status. Protein-bound Hcy increases up to a maximum capacity of about 140 micromol/L, and there is a concurrent displacement of protein-bound cysteine. When the Hcy binding approaches saturation, free oxidized and reduced Hcy show a substantial increase. The resulting increase in reduced/total ratio for Hcy causes a parallel change in this ratio for the other aminothiols. These dynamics were observed during both chronic hyperhomocysteinemia (due to cobalamin deficiency or homocystinuria) and acute hyperhomocysteinemia (induced by methionine or Hcy loading). In addition, changes in redox thiol status have been observed in patients with vascular disease (decreased reduced/total ratio for cysteine), renal failure (low reduced/total ratio for aminothiols) or HIV infection (high level of reduced Hcy), which suggest primary imbalance between prooxidant and antioxidant processes in these patients. In conclusion, redox thiol status is a dynamic system which is probably linked to the extracellular antioxidant defence system. This must be taken into account when designing future experimental or epidemiological studies on Hcy and cardiovascular disease.
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PMID:Reduced, oxidized and protein-bound forms of homocysteine and other aminothiols in plasma comprise the redox thiol status--a possible element of the extracellular antioxidant defense system. 864 71

Previous studies have shown that elevated basal homocysteine levels are correlated among family members of patients with coronary vascular disease and juvenile venous thrombosis. This suggests the possibility of the presence of inherited basal mild hyperhomocysteinemia (mHH). We studied homocysteine levels, fasting as well as after methionine load, among 96 family members of 21 post-load hyperhomocysteinemic vascular index patients, i.e. 6 parents, 27 offspring, 38 siblings, 19 uncles and aunts and 6 cousins. In 15 out of 21 screened families post-load mHH was established in at least one family member. Fasting and post-load mHH was observed in 19 out of 89 (21%) screened family members (fasting homocysteine levels not measured in seven family members), and 31 out of 96 screened family members (32%), respectively. In 40% of all family members, post-load mHH was not accompanied by fasting mHH. We conclude that both fasting and post-load mHH seems to be inherited in the majority of hyperhomocysteinemic vascular patients.
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PMID:Prevalence of familial mild hyperhomocysteinemia. 883 29


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