vitamin-b-12 and Arteriosclerosis

A century ago a fat-soluble vitamin from leafy vegetables, later named vitamin E, was discovered to enhance fertility in animals. Vitamin E consists of 8 isomers of tocopherols and tocotrienols, each containing chromanol groups that confer antioxidant properties and differ only in the 15-carbon saturated phytyl poly-isoprenoid side chain of tocopherols and the 15-carbon unsaturated farnesyl poly-isoprenoid side chain of tocotrienols. Although tocotrienol was first isolated from rubber plants in 1964, its importance in multiple disease processes was not recognized until two decades later, when the cholesterol-lowering and anti-cancer effects were first reported. Tocotrienol (T3) protects against radiation injury and mitochondrial dysfunction by preventing opening of the mitochondrial permeability transition pore, thereby inhibiting loss of the active site for oxidative phosphorylation, thioretinaco ozonide oxygen ATP, from mitochondria by complex formation with the active site, TR

Topics: Aging; Animals; Arteriosclerosis; Cholesterol; Diterpenes; Homocysteine; Humans; Mitochondria; NAD; Neoplasms; Neurodegenerative Diseases; Oxidation-Reduction; Oxidative Phosphorylation; Permeability; Squalene; Tocotrienols; Vitamin B 12

Moderate hyperhomocysteinemia is one of risk factors for arteriosclerotic disease. In diabetic patients, hyperhomocysteinemia is an independent risk factor for macroangiopathy and mortality. Homocysteinemia is also associated with diabetic microangiopathy, silent stroke, and cognitive impairment. However, excluding those with nephropathy or microangiopathy, plasma homocysteine is lower in diabetic patients than non-diabetic controls. Oral treatment with folic acid, vitamin B12 and B6 reduces plasma homocysteine concentration about by 30%. The vitamin treatment for reduction of hyperhomocysteinemia improves endothelial dysfunction and retards carotid atherosclerosis. Few randomized control trials have showed a positive effect of the vitamin treatment on prevention from stroke and ischemic heart disease. Further prospective intervention studies are necessary to address the issue whether lowering homocysteine does prevent the development and progression of diabetic macroangiopathy.

Topics: Arteriosclerosis; Diabetic Angiopathies; Folic Acid; Humans; Hyperhomocysteinemia; Randomized Controlled Trials as Topic; Risk Factors; Vitamin B 12; Vitamin B 6

The nutritional status and plasma concentrations of some group B vitamins, namely vitamin B6, vitamin B12 and folic acid, have recently emerged as inverse correlates of cardiovascular risk, and several experimental and clinical studies, these latter mostly retrospective and case-control studies, indicate a defect of such vitamins as capable of promoting the progression of atherosclerosis. Since all these vitamins are implicated in homocysteine metabolism, and since homocysteine has a well-recognized relationship with cardiovascular risk, the simplest hypothesis to explain the relationship of vitamin B6, vitamin B12 and folic acid on the one hand, and cardiovascular risk on the other is that this relationship is mediated by plasma levels of homocysteine. The most convincing literature data for the existence of a relationship with cardiovascular risk are for vitamin B6 and folic acid. These vitamins, however, have also a series of in vitro effects indicating a direct antiatherogenic action, and the results of several clinical studies, especially for vitamin B6, indicate an inverse relationship with cardiovascular risk at least in part independent of homocysteinemia. A further confirmation of these data is important to devise future intervention strategies in primary and secondary prophylaxis of atherosclerotic vascular disease.

Topics: Adult; Aged; Arteriosclerosis; Cardiovascular Diseases; Case-Control Studies; Clinical Trials as Topic; Cross-Over Studies; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Male; Middle Aged; Multivariate Analysis; Primary Prevention; Prospective Studies; Retrospective Studies; Risk; Risk Factors; Time Factors; Treatment Outcome; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Fenofibrate is among the drugs of choice for treatment of hypertriglyceridaemia and low levels of high-density lipoprotein (HDL)-cholesterol, both recognised as risk factors for cardiovascular disease. Recently, a number of studies have shown an elevation of homocysteine levels with fenofibrate or bezafibrate therapy. Homocysteine is an atherogenic amino acid derived from the methionine cycle. At present, the underlying mechanism for this elevation has not been elucidated. While deterioration of vitamin status does not seem to be involved, impairment of renal function or changes in creatine metabolism are regarded as probable mechanisms. In patients not receiving lipid-lowering drugs, vitamin supplementation with folic acid and vitamin B12 effectively reduces the plasma homocysteine level. Two studies have shown that addition of folic acid or a vitamin combination to fenofibrate prevented most of the homocysteine increase associated with fenofibrate. Although the consequence of increasing homocysteine levels for cardiovascular risk has not been proven at present, it has to be considered that fenofibrate will be given for long-term treatment. Therefore, addition of folic acid and vitamin B12 to fenofibrate can be recommended to prevent the increase of homocysteine associated with fenofibrate, or treatment could be changed to gemfibrozil, which does not increase plasma homocysteine levels.

Topics: Arteriosclerosis; Fenofibrate; Folic Acid; Humans; Hyperhomocysteinemia; Hypolipidemic Agents; Kidney; Vitamin B 12

In the results numerouses clinical and epidemiological trials have shown that high level of blood homocysteine is a marker of increased risk of coronary, cerebral and peripheral atherosclerosis. Close relation between high level of homocysteine and enhanced platelet aggregation, its prooxidant action, ability to inhibit growth of endothelial cells constituted basis for proposal of homocysteine theory of atherosclerosis. In this review use soy, products its processing, folate and vitamins B6 and B12 as homocysteine reducing therapy has been also suggested in the treatment of the patients with cardiovascular diseases.

Topics: Alcoholic Beverages; Arteriosclerosis; Cardiovascular Diseases; Clinical Trials as Topic; Coronary Disease; Diet; Female; Folic Acid; Glycine max; Homocysteine; Humans; Hyperhomocysteinemia; Male; Platelet Aggregation; Risk Factors; Vitamin B 12; Vitamin B 6

An increased plasma level of homocysteine has been proposed as an independent risk factor for atherosclerosis; this review examines the evidence.. A Medline search was undertaken for English language articles on homocysteine and vascular disease. Further papers were identified by cross-referencing from the reference lists of relevant major articles.. Although much interest has been generated about homocysteine and atherosclerotic disease, contradictory data exist regarding its role in disease progression. There is insufficient current evidence to regard increased homocysteine level as a causative factor in atherosclerotic disease.. It is not known whether lowering plasma homocysteine concentration will reduce cardiovascular risk in the long term. Until such data become available, there is no evidence for the widespread use of folic acid therapy to reduce cardiovascular disease risk.

Topics: Arteriosclerosis; Diet; Folic Acid; Homocysteine; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Oxidoreductases Acting on CH-NH Group Donors; Risk Factors; Vitamin B 12

Plasma homocyst(e)ine level is a strong independent risk factor for vascular disease. The spelling of homocyst(e)ine reflects that what is measured, and what constitutes the risk factor; it includes homocysteine, homocystine (the dimer of homocysteine) and mixed cysteine-homocysteine disulfide. Homocyst(e)ine levels above 10.2 micro mol/L are associated with a doubling of coronary risk, and levels above 20 micro mol/L are associated with a 9.9-fold increase in risk compared with levels below 9 micro mol/L. The mechanisms by which homocyst(e)ine promotes vascular disease include increased thrombosis, consumption of nitric oxide, endothelial injury, and reduced thrombolysis. Homocyst(e)ine is an independent predictor of carotid atherosclerosis. Vitamin therapy with folate, pyridoxine (vitamin B(6)), and cyanocobalamin (vitamin B(12)) reduces blood levels of homocyst(e)ine, improves endothelial function, reduces levels of fibrinogen and lipoprotein(a), improves thrombolysis, and in uncontrolled clinical observation, leads to regression of carotid plaque. These lines of evidence support a causal relationship between homocyst(e)ine and atherosclerosis, and suggest that in patients with vascular disease, an appropriate target level for therapy may be below 9 or 10 micro mol/L. Randomized controlled studies are under way to determine whether vitamin therapy is effective in secondary prevention of myocardial infarction and stroke.

Topics: Arteriosclerosis; Clinical Trials as Topic; Dipeptides; Folic Acid; Homocysteine; Homocystine; Humans; Pyridoxine; Risk Factors; Vitamin B 12

Topics: Adult; Arteriosclerosis; Child; Child, Preschool; Coronary Disease; Endothelium, Vascular; Folic Acid; Humans; Hyperhomocysteinemia; Risk Factors; United Kingdom; Vitamin B 12

Homocysteine is an amino acid that plays a key role in methionine- and homocysteine metabolism. Homocystinuria has been described about four decades ago to be an inherited (autosomal recessive) disorder with rapid progressive atherosclerosis. Thus, homocysteine has been investigated intensively with respect to vascular wall injury and atherogenesis. Folic acid and vitamin B12 are cofactors of methioninsynthase, a key enzyme in homocysteine metabolism. Plasma levels of homocysteine are higher in patients with coronary artery disease documented by coronary angiography than in individuals with normal coronary arteries. Supplementation of folic acid is the treatment of choice to lower plasma homocysteine concentrations. Improvement in endothelial function could be documented in patients with folic acid supplementation. Large scaled clinical trials investigating folic acid supplementation in secondary prevention are now in progress. Today, homocysteine and its association with atherosclerosis raise a lot of questions to be answered. A distinct pathophysiological model linking hyperhomocysteinaemia and atherosclerosis is still not available. The presence of hyperhomocysteinemia in atherosclerotic vascular disease as a surrogate with no pathophysiological relevance itself cannot be ruled out. Routine testing of homocysteine levels is not yet recommended. Treatment of patients with folic acid or vitamin B for primary and secondary prevention of atherosclerotic vascular disease cannot be recommended today, because large scaled intervention trials on homocysteine lowering by vitamin B or folic acid are not available yet. Possible effects of these interventions on acute vascular events are not known.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Animals; Arteriosclerosis; Clinical Trials as Topic; Coronary Artery Disease; Disease Models, Animal; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Models, Biological; Vitamin B 12

Elevated plasma homocysteine is a new risk factor for atherosclerotic vascular disease resulting in progressive atherogenesis in the arteries of the limbs, the coronary arteries and the cerebrovascular system. Hyperhomocysteinemia may be induced by failure or decreased enzyme activity of the cystathionine-beta-synthase and methylenetetrahydrofolate reductase due to genetic mutation or deficiency of folic acid, vitamin B12 and vitamin B6. Oxidation of homocysteine to homocystine is accompanied with production of hydrogen peroxide inducing damage of endothelium through oxidative stress. The injury of the endothelium by homocysteine can be shown by measuring flow-induced vasodilation in men. The abnormalities of coagulation found in hyperhomocysteinemia is related to the impairment of the function of endothelial cells and inhibition of the thrombomodulin-protein C and glycosaminoglycan-antithrombin-III anticoagulant system. Homocysteine decreases the level of glutathione peroxidase in the endothelial cells, and inhibits its activation leading to the impairment of oxidative defensive mechanism, and to the free radical-induced NO-inactivation. In decreasing of plasma homocysteine level and preventing its influence on endothelium, moreover in improving of endothelial function the folic acid has cardinal importance, however the vitamin B12 and vitamin B6 also play role in the maintenance of normal homocysteine level of blood.

Topics: Antioxidants; Arteriosclerosis; Disease Progression; Endothelium, Vascular; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Oxidative Stress; Risk Factors; Thrombosis; Treatment Outcome; Vitamin B 12; Vitamin B 6

To establish guidelines for the screening and treatment of hyperhomocysteinemia in the investigation and management of coronary artery disease (CAD).. Measurement of plasma total homocysteine (tHcy) levels in the fasting state or 4-6 hours after oral methionine load; vitamin supplementation with folic acid and vitamins B6 and B12; adherence to the recommended daily allowance of dietary sources of folate and vitamins B6 and B12.. This article reviews the available evidence on the association between plasma tHcy levels and CAD and the effect of lowering tHcy levels through vitamin supplementation or dietary intake.. MEDLINE was searched for relevant English-language articles published from January 1966 to June 1999; also reviewed were additional articles identified from the bibliographies.. Cardiovascular disease is the leading cause of death in Canada. Homocysteine, generated in the metabolism of methionine, may have a role in the development of cardiovascular disease. The prevalence of hyperhomocysteinemia in the general population is between 5% and 10% and may be as high as 30%-40% in the elderly population. If population-based studies are correct, tHcy may be responsible for up to 10% of CAD events and thus may represent an important and potentially modifiable risk factor for cardiovascular disease. Laboratory testing for tHcy is currently restricted to research centres, and costs range from $30 to $50 per person. Newer, less costly techniques have been developed and should become readily available with time.. The strength of evidence was evaluated using the methods of the Canadian Task Force on Preventive Health Care.. Although there is insufficient evidence to recommend the screening or management of hyperhomocysteinemia at present (grade C recommendation), adherence to recommended daily allowance of dietary sources of folate and vitamins B12 and B6 should be encouraged. If elevated tHcy levels are discovered, vitamin deficiency should be ruled out to allow specific treatment and prevention of complications, such as neurological sequelae due to vitamin B12 deficiency. Experts in the field advocate treatment of elevated tHcy levels in high-risk people, such as those with a personal or family history of premature atherosclerosis or a predisposition to develop hyperhomocysteinemia. Definitive guidelines for the management of hyperhomocysteinemia await the completion of randomized trials to establish the effect of vitamin supplementation on CAD events.. The findings of this analysis were reviewed through an iterative process by the members of the Canadian Task Force on Preventive Health Care.. The Canadian Task Force on Preventive Health Care is funded through a partnership between the Provincial and Territorial Ministries of Health and Health Canada.

Topics: Aged; Arteriosclerosis; Canada; Coronary Disease; Dietary Supplements; Disease Susceptibility; Fasting; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Mass Screening; Methionine; Preventive Medicine; Pyridoxine; Randomized Controlled Trials as Topic; Risk Factors; Vitamin B 12

Numerous studies report strong associations between hyperhomocysteinemia and premature atherosclerotic vascular disease. Causes of hyperhomocysteinemia are hereditary heterozygous or, in very rare cases, homozygous defects, and quite frequently a lack of the coenzymes B6 and B12 and the cosubstrate folate. Lifestyle factors, age, sex, acute and chronic illness, vitamin deficiency and certain drugs may elevate homocysteine concentrations. Vitamin B supplementation, especially folic acid, is an effective treatment of hyperhomocysteinemia. Clinical trials are required to confirm the potential benefit of lowering homocysteine in regard of the development and progression of atherosclerotic vascular disease. The relevance of hyperhomocysteinemia as a risk factor for atherosclerosis, in contrast to the classical triad of risk factors, namely hypercholesterolemia, smoking and hypertension, is still unknown. Furthermore, a lack of standardized analytical methods for the determination of both homocysteine and blood folate renders the evaluation of studies and clinical data difficult. Therefore, at present, diagnosis and treatment is only recommended in high-risk patients (strong family history of premature atherosclerosis or arterial occlusive disease, especially in the absence of other risk factors, as well as in members of their families) with hyperhomocysteinemia.

Topics: Arteriosclerosis; Case-Control Studies; Coronary Disease; Folic Acid; Hematinics; Humans; Hyperhomocysteinemia; Prospective Studies; Pyridoxine; Retrospective Studies; Risk Factors; Vitamin B 12

Evidence of a positive association between mild hyperhomocysteinemia and arterial vascular disease has been accumulating in the last decade. Mild hyperhomocysteinemia acts as an independent vascular risk factor with equal strength as hypercholesterolemia and smoking. If jointly present with hypertension and smoking, its effect seems synergistic. This could make the outcome of homocysteine-lowering intervention beneficial, particularly in cases with concomitance of conventional vascular risk factors. So far, however, data on the clinical outcome of homocysteine-lowering treatment with a simple, safe, and cheap vitamin regimen are lacking. Trials investigating a beneficial clinical effect of homocysteine-lowering treatment using folic acid in a dose ranging from 0.2 to 5 mg daily, alone or in combination with vitamin B12 with or without vitamin B6 versus placebo, are ongoing. Furthermore, exploration of the unifying mechanism by which increased homocysteine levels may lead to both arterial and venous occlusions is warranted. These lines of investigations have to provide the ultimate proof of causality of hyperhomocysteinemia in vascular disease in the near future.

Topics: Arteriosclerosis; Case-Control Studies; Clinical Trials as Topic; Comorbidity; Coronary Disease; Folic Acid; Genetic Predisposition to Disease; Humans; Hyperhomocysteinemia; Hypertension; Meta-Analysis as Topic; Multicenter Studies as Topic; Oxidative Stress; Pyridoxine; Risk Factors; Smoking; Vitamin B 12

Hyperhomocysteinemia refers to an elevated circulating level of the sulfur-containing amino acid homocysteine and has been shown to be a risk factor for vascular disease in the general population. In patients with renal failure, hyperhomocysteinemia is a common feature. The underlying pathophysiological mechanism for this phenomenon is unknown. Proposed mechanisms include reduced renal elimination of homocysteine and impaired nonrenal disposal, possibly because of inhibition of crucial enzymes in the methionine-homocysteine metabolism by the uremic milieu. Absolute or relative deficiencies of folate, vitamin B6, or vitamin B12 may also play a role. Several case-control and prospective studies have now indicated that hyperhomocystenemia is an independent risk factor for atherothrombotic disease in patients with predialysis and end-stage renal disease. In renal patients, plasma homocysteine concentration can be reduced by administration of folic acid in doses ranging from 1 to 15 mg per day. In more than 50% of the cases, however, the homocysteine concentration remains above 15 micromol/L. The effects of vitamin B12 or vitamin B6 are unclear. Large intervention trials are now needed to establish whether homocysteine-lowering therapy will reduce atherothrombotic events in patients with renal failure. These studies are now planned or are ongoing.

Topics: Adult; Arteriosclerosis; Cardiovascular Diseases; Case-Control Studies; Child; Endothelium, Vascular; Female; Folic Acid; Folic Acid Deficiency; Follow-Up Studies; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Life Tables; Male; Methionine; Peritoneal Dialysis; Prospective Studies; Pyridoxine; Renal Dialysis; Survival Analysis; Thrombophilia; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6 Deficiency

High plasma levels of homocysteine are the results of the interplay between congenital and environmental factors. In the last two decades, a growing amount of interest has focused on mild-to-moderate hyperhomocysteinemia as a risk factor of thromboembolic diseases. Case-control and cross-sectional studies clearly indicated that mild-to-moderate hyperhomocysteinemia is associated with heightened risk of both arterial and venous thrombosis. On the other hand, prospective studies did not unequivocally show that hyperhomocysteinemia is associated with a high thrombotic risk. Therefore, additional studies are needed to define whether hyperhomocysteinemia is a risk factor for thrombosis, especially of the venous circulation. Among these, prospective cohort studies will clarify better the temporal relationship between high homocysteine levels and the thrombotic event. Most importantly, however, randomized, placebo-controlled, double-blind trials of the effects of homocysteine-lowering vitamins on the thrombotic risk are urgently needed. Not only will they help in defining whether the relationship between hyperhomocysteinemia and thrombosis is causal, they will also have a potential dramatic impact in the prevention of thromboembolic events.

Topics: Adult; Aged; Animals; Arteriosclerosis; Avitaminosis; Case-Control Studies; Clinical Trials as Topic; Cohort Studies; Cross-Sectional Studies; Cystathionine beta-Synthase; Female; Folic Acid; Gene Frequency; Homocysteine; Homocystinuria; Hormone Replacement Therapy; Humans; Hyperhomocysteinemia; Male; Methionine; Methylation; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Muscle, Smooth, Vascular; Oxidoreductases Acting on CH-NH Group Donors; Prevalence; Primates; Prospective Studies; Pyridoxine; Risk Factors; Smoking; Tamoxifen; Thrombophilia; Thrombosis; Vitamin B 12

In recent years there has been growing evidence that high levels of plasmatic homocysteine constitute an independent risk factor for early cardiovascular disease. In this article we review the main theories of atherosclerosis which take into account the proteins, namely homocysteine, homocysteine metabolism, the cause that may be responsible for high levels of homocysteinemia, the pathophysiologic mechanisms of vascular lesion induced by hyperhomocysteinemia, the clinical evidence that homocysteinemia constitutes a vascular risk factor and finally, the evidence that it is possible to control homocysteinemia with supplementation of co-factors of homocysteine metabolism, namely vitamin B6, B12 or folic acid.

Topics: Arteriosclerosis; Cardiovascular Diseases; Folic Acid; Humans; Hyperhomocysteinemia; Pyridoxine; Risk Factors; Vitamin B 12

Homocystinuria is an uncommon genetic disease characterized by a marked increase of serum homocysteine (HCY), an intermediate of methionine metabolism. In patients with homocystinuria, hyperhomocysteinemia promotes the development of atherosclerotic lesions and is responsible for premature coronary artery disease. Recently, several studies have also demonstrated that moderate hyperhomocysteinemia--not necessarily linked to an inborn metabolic defect--may also be considered as an independant risk factor for cardiovascular disease. The main mechanisms of HCY atherogenic action are thought to be LDL oxydation, inhibition of vascular endothelium growth combined with stimulation of smooth muscular cells proliferation, and interference with the coagulation and fibrinolytic systems. Cofactors of key enzymes in HCY metabolism, folic acid, vitamin B12 and vitamin B6, may be given, alone or in combination, for the treatment of hyperhomocysteinemia. Homocysteinemia can be assessed by basal plasma HCY concentration and/or by HCY levels measured after a methionine loading test. Mainly measured till now in specialized laboratories using rather complex techniques (HPLC, GCMS, amino acid analyser ...), HCY determination is today spreading widely owing to the development of automated immunoassays.

Topics: Arteriosclerosis; Cardiovascular Diseases; Folic Acid; Homocystinuria; Humans; Hyperhomocysteinemia; Pyridoxine; Risk Factors; Vitamin B 12

Homocysteine is a sulfur-containing amino acid intermediate involved in two metabolic pathways, in the remethylation to methionine and in the transsulfuration to cysteine. Severe hyperhomocysteinemia (> 100 mumol/l) is found in congenital homocystinuria. Moderate (15-30 mumol/l) or intermediate (> 30-100 mumol/l) hyperhomocysteinemia is caused by defects in genes encoding for enzymes of homocysteine metabolism or by inadequate intake of those vitamins that are involved in homocysteine metabolism (folic acid, cobalmin, and vitamin B6). Today, hyperhomocysteinemia should be considered an important risk factor for atherosclerotic vascular and venous thromboembolic diseases. Homocysteine-plasma levels above the 95th percentile were found to be associated with a 2 to 3-fold elevated relative risk for deep-vein thrombosis and pulmonary embolism. Moreover, mild hyperhomocysteinemia has been shown to be associated with a 2 to 4-fold increased relative risk for coronary artery disease, cerebrovascular disease, and peripheral arterial occlusive disease. Several mechanisms have been proposed by which hyperhomocysteinemia contributes to atherogenesis and thrombogenesis. Several studies have shown that hyperhomocysteinemia can be corrected by supplementation of folic acid, cobalamin and vitamin B6. Clinical trials are urgently needed which investigate the preventive effect of supplementation of these vitamins on thrombotic diseases.

Topics: Arteriosclerosis; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Pyridoxine; Risk Factors; Thromboembolism; Vitamin B 12

An elevated level of total homocysteine (tHcy) in blood, denoted hyperhomocysteinemia, is emerging as a prevalent and strong risk factor for atherosclerotic vascular disease in the coronary, cerebral, and peripheral vessels, and for arterial and venous thromboembolism. The basis for these conclusions is data from about 80 clinical and epidemiological studies including more than 10,000 patients. Elevated tHcy confers a graded risk with no threshold, is independent of but may enhance the effect of the conventional risk factors, and seems to be a particularly strong predictor of cardiovascular mortality. Hyperhomocysteinemia is attributed to commonly occurring genetic and acquired factors including deficiencies of folate and vitamin B12. Supplementation with B-vitamins, in particular with folic acid, is an efficient, safe, and inexpensive means to reduce an elevated tHcy level. Studies are now in progress to establish whether such therapy will reduce cardiovascular risk.

Topics: Arteriosclerosis; Cardiovascular Diseases; Coronary Artery Disease; Female; Folic Acid; Folic Acid Deficiency; Forecasting; Homocysteine; Humans; Intracranial Arteriosclerosis; Male; Peripheral Vascular Diseases; Prevalence; Risk Factors; Safety; Thromboembolism; Vitamin B 12; Vitamin B 12 Deficiency

Recently, elevated homocysteine blood concentrations have been identified as an independent risk factor for the development of atherosclerotic lesions. The amino acid homocysteine is metabolized in the human body involving the vitamins folic acid, B12 and B6 as essential cofactors and coenzymes, respectively. There is an inverse relationship between the status of the relevant B-vitamins and the homocysteine blood concentration. Supplementation of these vitamins results in a significant reduction of the homocysteine level. Nutritive amounts seem to be sufficient to obtain this reduction, even in the case of elevated homocysteine levels.

Topics: Arteriosclerosis; Coronary Disease; Folic Acid; Hematinics; Homocysteine; Humans; Middle Aged; Pyridoxine; Risk Factors; Vitamin B 12; Vitamin B Complex

Homocysteine is an intermediate amino acid formed during the metabolism of methionine, a sulfur-containing essential amino acid, and cleared by the kidneys. The two major acquired causes of increased homocysteine values are chronic renal failure and absolute or relative deficiencies of folate, vitamin B12 or vitamin B6, three vitamins involved in the normal metabolism of methionine. We studied 176 patients (97 men and 79 women with mean age 56.3 +/- 14.8 years) with end-stage renal disease on peritoneal or hemodialysis. Homocysteine concentrations averaged 26.6 +/- 1.5 mumol/liter in patients with renal failure as compared to 10.1 +/- 1.7 mumol/liter in normals. Abnormal values exceeded the 95th percentile for normal controls in 149 patients, giving an overall prevalence of homocysteinemia of 85%. There was preservation of the negative correlation between homocysteine and folate (r = -0.48), suggesting responsiveness in spite of impairment. Increased homocysteine concentrations were associated with an increased odds ration for atherosclerotic and thrombotic complications independent of other traditional risk factors and the length of time on dialysis. The odds ratio for vascular events with homocysteine levels was 2.9 (CI 1.4 to 5.8) for the upper two quintiles of homocysteine values compared to the lower three quintiles adjusted for age, gender, hypertension, diabetes, hypercholesterolemia, smoking and time on dialysis. These data indicate that plasma homocysteine values represent an independent risk factor for vascular events in patients on peritoneal and hemodialysis. The mechanism by which high homocysteine concentrations might cause vascular damage in patients with renal failure remains unclear.

Topics: Arteriosclerosis; Female; Folic Acid; Homocysteine; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Male; Methionine; Middle Aged; Pyridoxine; Thrombosis; Vitamin B 12

To determine the risk of elevated total homocysteine (tHcy) levels for arteriosclerotic vascular disease, estimate the reduction of tHcy by folic acid, and calculate the potential reduction of coronary artery disease (CAD) mortality by increasing folic acid intake.. MEDLINE search for meta-analysis of 27 studies relating homocysteine to arteriosclerotic vascular disease and 11 studies of folic acid effects on tHcy levels.. Studies dealing with CAD, cerebrovascular disease, and peripheral arterial vascular disease were selected. Three prospective and six population-based case-control studies were considered of high quality. Five cross-sectional and 13 other case-control studies were also included. Causality of tHcy's role in the pathogenesis of vascular disease was inferred because of consistency across studies by different investigators using different methods in different populations.. Elevations in tHcy were considered an independent graded risk factor for arteriosclerotic vascular diseases. The odds ratio (OR) for CAD of a 5-mumol/L tHcy increment is 1.6 (95% confidence interval [CI], 1.4 to 1.7) for men and 1.8 (95% CI, 1.3 to 1.9) for women. A total of 10% of the population's CAD risk appears attributable to tHcy. The OR for cerebrovascular disease (5-mumol/L tHcy increment) is 1.5 (95% CI, 1.3 to 1.9). Peripheral arterial disease also showed a strong association. Increased folic acid intake (approximately 200 micrograms/d) reduces tHcy levels by approximately 4 mumol/L. Assuming that lower tHcy levels decrease CAD mortality, we calculated the effect of (1) increased dietary folate, (2) supplementation by tablets, and (3) grain fortification. Under different assumptions, 13,500 to 50,000 CAD deaths annually could be avoided; fortification of food had the largest impact.. A 5-mumol/L tHcy increment elevates CAD risk by as much as cholesterol increases of 0.5 mmol/L (20 mg/dL). Higher folic acid intake by reducing tHcy levels promises to prevent arteriosclerotic vascular disease. Clinical trials are urgently needed. Concerns about masking cobalamin deficiency by folic acid could be lessened by adding 1 mg of cobalamin to folic acid supplements.

Topics: Arteriosclerosis; Coronary Disease; Female; Folic Acid; Food, Fortified; Homocysteine; Humans; Male; Pyridoxine; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

In an epidemiologic survey, a marginal status of folic acid, vitamin B12, and vitamin B6 was shown to be associated with hyperhomocysteinemia. In a case-control study, a low plasma folate concentration was associated with increased coronary heart disease risk. This phenomenon appears to be mediated by folate's effect on homocysteine metabolism. Both studies offer further perspectives on homocysteine as an atherogenic risk factor.

Topics: Arteriosclerosis; Case-Control Studies; Coronary Disease; Folic Acid; Homocysteine; Humans; Nutritional Status; Pyridoxine; Risk Factors; Vitamin B 12

Reduction of circulating homocysteine levels by folic acid suggests an additional approach to the prophylaxis of certain forms of vascular disease related to atherogenic amino acids.

Topics: Arterial Occlusive Diseases; Arteriosclerosis; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Metabolism, Inborn Errors; Vascular Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Adult; Age Factors; Aged; Angina Pectoris; Arteriosclerosis; Body Weight; Child; Cholesterol; Feces; Female; Follow-Up Studies; Forecasting; Heart; Heart Function Tests; Humans; Hyperlipidemias; Ileum; Intestinal Absorption; Intestine, Small; Lipoproteins; Male; Methods; Middle Aged; Myocardial Infarction; Postoperative Complications; Triglycerides; Vitamin B 12; Water-Electrolyte Balance; Xanthomatosis

Topics: Antimetabolites; Arteriosclerosis; Ascorbic Acid; Cholesterol; Choline; Corrinoids; Ethyl Biscoumacetate; Heparin; Humans; Hypercholesterolemia; Iodoacetates; Lipotropic Agents; Magnesium Sulfate; Neomycin; Niacin; Nicotinic Acids; Progesterone; Pyridoxine; Thyroxine; Triparanol; Vitamin B 12

We previously demonstrated among renal-transplant recipients (RTRs) a high prevalence of hyperhomocysteinemia, which might account for their elevated cardiovascular risk. The purpose of our study was to document, in hyperhomocysteinemic RTRs, the effect of vitamin supplementation on carotid intima-media thickness (cIMT), which is an early sign of atherosclerosis.. A total of 56 stable hyperhomocysteinemic RTRs were randomly assigned to vitamin supplementation (folic acid 5 mg/day; vitamin B(6) 50 mg/day; vitamin B(12) 400 microg) (group A) or placebo treatment (group B) for 6 months. All subjects underwent cardiovascular risk-factor assessment, including fasting homocysteine (Hcy) levels assay, and high resolution B-mode ultrasound to measure the intima-media thickness of common carotid arteries, at time of enrollment and after 6 months.. Fasting Hcy levels markedly decreased in group A after treatment (21.8 [15.5-76.6] micromol/L vs. 9.3 [5.8-13] micromol/L; P<0.0001), whereas no significant changes were observed in group B (20.5 [17-37.6] micromol/L vs. 20.7 [15-34] micromol/L; P=not significant). In group A, cIMT significantly decreased after treatment (0.95+/-0.20 mm vs. 0.64+/-0.17 mm; P<0.0001). All except one patient showed a reduction of cIMT and the mean percentage of cIMT decrease was -32.2+/-12.9%. Patients with methylenetetrahydrofolate reductase (MTHFR) C677T +/+ genotype, with higher Hcy levels, had the major percentage of decrease of Hcy with respect to the other genotypes (mean decrease: MTHFR +/+ 74.8+/-5.7%; MTHFR +/- 58.1+/-10%; MTHFR -/- 56.3+/-8.6%). In hyperhomocysteinemic patients without vitamin supplementation (group B) we documented a significant increase in cIMT after 6 months (0.71+/-0.16 mm vs. 0.87+/-0.19 mm; P<0.05). In 19 of 28 subjects we observed an increase in cIMT, and in 9 of 28 the cIMT was unmodified. The mean percentage of cIMT increase was + 23.3+/-21.1%.. Our results demonstrate a beneficial effect of the treatment of hyperhomocysteinemia by vitamin supplementation on cIMT in a group of RTRs.

Topics: Adult; Arteriosclerosis; Carotid Arteries; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Humans; Hyperhomocysteinemia; Male; Middle Aged; Prospective Studies; Pyridoxine; Tunica Intima; Vitamin B 12

Hyperhomocysteinemia is a risk factor for atherothrombosis. Through unknown mechanisms, individuals with type 2 diabetes appear particularly susceptible. We determined whether components of homocysteine metabolism are associated with intima-media thickness in individuals with and without type 2 diabetes.. In a cross-sectional design, we studied 231 Caucasian individuals, 60.6% having type 2 diabetes. We measured fasting homocysteine, vitamin B6 and vitamin B12 in plasma, and folate, S-adenosylmethionine and S-adenosylhomocysteine in plasma and erythrocytes. A homocysteine concentration >12 micromol/l was associated with a greater intima-media thickness of +0.07 mm (95% CI, +0.01 to +0.13; P=0.03) among diabetic individuals and of -0.004 mm (95%CI, -0.08 to +0.07; P=0.92) among non-diabetic individuals. An erythrocyte S-adenosylmethionine concentration above >4000 nmol/l was associated with a smaller intima-media thickness of -0.04 mm (95%CI, -0.10 to +0.02; P=0.17) for diabetic individuals versus -0.12 mm (95%CI, -0.20 to -0.36; P=0.005) for non-diabetic individuals.. With regard to carotid intima-media thickness, individuals with diabetes appear more susceptible to the detrimental effects of homocysteine than non-diabetic individuals. In addition, diabetic individuals may lack the protective effect on the vascular wall conferred by high concentrations of S-adenosylmethionine. These findings may help explain why hyperhomocysteinemia is an especially strong risk factor for atherothrombosis among individuals with type 2 diabetes.

Topics: Aged; Arteriosclerosis; Carotid Arteries; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Erythrocytes; Female; Homocysteine; Humans; Male; Middle Aged; S-Adenosylmethionine; Tunica Intima; Tunica Media; Vitamin B 12; Vitamin B 6

Hyperhomocysteinemia is associated with arterial hypertension and endothelial dysfunction in healthy humans. Placebo-controlled vitamin intervention studies cannot distinguish intrinsic actions of homocysteine (tHcy) and folate concentrations on the endothelium. The present two-period crossover study investigates the effects of tHcy lowering through oral folic acid on antioxidant status and resistance vessel reactivity in patients with established coronary artery disease (CAD). We investigated 27 male patients with angiographically documented multivessel CAD aged 50 (range 46-56) years. Resistance vessel reactivity was assessed by measurement of postischemic reactive hyperemia (RH) in the forearm using venous occlusion plethysmography at baseline, after 6 weeks of treatment with 5 mg of oral folic acid, and after a washout period of another 6 weeks. Plasma folate increased 3.49-fold with a mean tHcy reduction of 21.3%. Peak reactivity of resistance vessels improved significantly (18.97-23.60 ml/min(-1) per 100 ml; P = 0.01) with unchanged total antioxidant status (TAS; 0.912-0.944 microM; P = 0.4). This effect was limited to subjects (n = 14) with a tHcy reduction >2 microM (median reduction, 14.4-9.6 microM, P < 0.001). In the 13 subjects with a below-median reduction, tHcy remained unaltered (9.7-9.6 microM, P = 0.88) and TAS increased significantly (0.923-1.055 microM, P = 0.006), whereas RH peak flow was not affected (20.22-22.99 ml/min(-1) per 100 ml, P = 0.28). Homocysteine lowering >2 microM through folic acid supplementation improves resistance vessel reactivity in patients with CAD. Our data support the hypothesis that homocysteine lowering may have intrinsic vasoprotective effects largely independent of folate.

Topics: Arteriosclerosis; Blood Flow Velocity; Cholesterol; Coronary Disease; Cross-Over Studies; Folic Acid; Forearm; Homocysteine; Humans; Male; Middle Aged; Placebos; Regional Blood Flow; Triglycerides; Vascular Resistance; Vitamin B 12

Homocysteine is a proposed causal risk factor for atherosclerosis, but this remains controversial. We measured fasting plasma homocysteine concentrations immediately after atherothrombotic stroke and in the convalescent period to investigate this controversy.. One hundred six patients (59 men and 47 women, mean age 57.2 [25 to 70] and 56.5 [26 to 69] years, respectively) were recruited within 24 hours of admission, and 82 patients were resampled at least 3 months later. Fasting total plasma homocysteine (tHcy) concentrations were measured by high-performance liquid chromatography.. Median tHcy in the acute phase of stroke was not significantly higher than in matched control subjects (men 9.2 [range 4.4 to 22.8] versus 8.7 [4.9 to 20] micromol/L, P:=0.09, Mann-Whitney U: test; women 8.1 [4.8 to 32.3] versus 7.6 [3.3 to 14.4] micromol/L, P:=0.58). Median plasma concentrations increased significantly in the convalescent period (from 8.5 [4.8 to 19.2] to 10.1 [4.3 to 31.5] micromol/L, P:<0.001, Wilcoxon signed rank test) and were then significantly higher than in control subjects in both men and women (P:=0.03 and 0.05, respectively, Mann-Whitney U: test). This did not appear to be explained by alteration in the known covariates red-cell folate, serum B(12), or creatinine concentrations.. Homocysteine concentrations are not elevated after recent atherothrombotic stroke but rise in the convalescent period. These data do not support the hypothesis that raised plasma homocysteine concentrations predate atherothrombotic stroke. Instead, they offer an explanation for the discrepancies between prospective and retrospective studies and suggest that elevated tHcy levels may be caused by the disease process itself.

Topics: Acute Disease; Adult; Aged; Arteriosclerosis; Brain; Case-Control Studies; Chromatography, High Pressure Liquid; Convalescence; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Intracranial Thrombosis; Lipids; Male; Middle Aged; Regression Analysis; Risk Factors; Scotland; Stroke; Stroke Rehabilitation; Tomography, X-Ray Computed; Vitamin B 12

Ischemic heart disease and other complications of atherosclerosis are the usual cause of death in patients with chronic renal failure. Important factors associated with early onset of atherosclerosis in these patients are hyperhomocysteinemia, hyperfibrinogenemia, and elevated levels of lipoprotein(a) (Lp(a)). Folic acid (15 mg/d), pyridoxine (150 mg/d), and cyanocobalamin (1 mg/wk) were administered for 4 weeks in 21 patients receiving dialysis, and a simultaneous, statistically significant reduction in the concentration of homocysteine, fibrinogen, and Lp(a) was found. A positive correlation between decreasing homocysteine and fibrinogen levels was also noted. The parameters studied approached presupplementation values 6 months after vitamins were discontinued. The results suggest that vitamin supplementation has a favorable effect on risk factors of atherosclerosis in patients with renal failure and that interactions may exist between homocysteine, fibrinogen, and Lp(a).

Topics: Adult; Arteriosclerosis; Cholesterol; Creatinine; Drug Therapy, Combination; Female; Fibrinogen; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Lipoprotein(a); Male; Pyridoxine; Renal Dialysis; Risk Factors; Triglycerides; Urea; Uric Acid; Vitamin B 12; Vitamin B Complex

Moderate hyperhomocysteinemia is an atherogenic risk factor and plays an important role in geriatrics. Here, we have investigated the role of hyperhomocysteinemia in two elderly groups: 104 longeval subjects of 85-102 years, 100 seniors aged 65-75 years, and 75 controls of 19-60 years. Elevated homocysteine levels were found in 58% of longeval subjects in comparison with 32% in seniors. The homocysteine level in serum correlated positively with age as well as serum creatinine, and inversely with serum folate, but there was no correlation with serum B-vitamins. The frequency of vitamin B deficiency in serum of longeval subjects compared to seniors was as follows: vitamin B6 43% vs. 22%, vitamin B12 20% vs. 8%, and folic acid 1% in both groups. Increased serum creatinine levels (> 1.1 mg/dl) were found in 63% of the longeval subjects and in 32% of seniors. The 677-missense mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, responsible for moderate homocysteine elevation, was found in 35, 37 and 27% of alleles in longeval persons, senior subjects and younger controls, respectively, showing no significant difference in frequency distributions of the MTHFR gene mutation. It can be concluded that hyperhomocysteinemia is very common with increased age. Its importance as an atherogenic risk factor with advanced age has to be clarified.

Topics: Adult; Aged; Aged, 80 and over; Aging; Arteriosclerosis; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Function Tests; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Multivariate Analysis; Mutation; Oxidoreductases Acting on CH-NH Group Donors; Regression Analysis; Risk Assessment; Risk Factors; Statistics, Nonparametric; Vitamin B 12

A group of 173 patients with the diagnosis of systemic arteriosclerosis received a treatment with Novocain, according to the following schedule: three times a week intramusculary injections of 2% procain 5ml, that means 12 injections a month in 3--5 series. The results were very encouraging in 46% of the treated patients, in 28% a slight improvement was obtained while in 26% the state was unchanged but not worse. The treatment with Gerovital H3 according to A. Aslans method gave very good results in the treatment of diseases like: heart ischemia, systemic arteriosclerosis, predominant cerebral arteriosclerosis, arteriosclerotic Parkinsons disease; obvious results were also obtained in the treatment of psychical disturbances related to arteriosclerosis. The comparison with the control group (patients with placebo) emphasized the good results of the treatment of Aslan: Gerovital H3.

Topics: Aged; Arteriosclerosis; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Humans; Injections, Intramuscular; Middle Aged; Placebos; Procaine; Vitamin B 12

Rates of renal and cardiovascular disease are high among Aboriginal Australians living in remote communities. Nutritional problems, in particular low folate levels, are also common. This suggests that increased homocysteine concentrations might be widespread, and a possible contributor to the high rates of cardiovascular disease.. To examine homocysteine concentrations, and their relationships to folate levels, and to markers of renal disease and cardiovascular disease in a remote Aboriginal Australian community. As part of a cross-sectional survey among adults in one community, homocysteine concentrations, concentrations of the crucial determinants (red blood cell (RBC) folate, vitamin B(12) and the C677T methylene tetrahydrofolate reductase polymorphism) and cardiovascular risk factors were examined.. Among 221 people, geometric mean homocysteine concentration was 11.8 micromol/L (range: 11.1-12.5 micromol/L), with 57/221 (26%) values > or =15.0 micromol/L. Higher concentrations were associated with older age, male gender, lower RBC folate and lower vitamin B(12) concentrations and homozygosity for C677T. Homocysteine concentrations were not related to the presence of albuminuria, other than over the overt albuminuria range. Homocysteine concentrations were inversely correlated with calculated glomerular filtration rate (GFR). Carotid intima-media thickness, however, was not related to homocysteine concentration. In multivariate analyses, age, male gender, lower RBC folate concentrations, lower vitamin B(12) concentrations, lower calculated GFR and the C677T polymorphism were all associated with homocysteine concentrations.. Homocysteine concentrations were consistent with previous limited reports in Aboriginal communities. Although superficially they are similar to reports from non-Aboriginal settings, the younger age of this cohort and the association of homocysteine concentrations with age suggest that age-specific concentrations are higher among Aboriginal Australians. In addition to dietary determinants, the high prevalence of apparently reduced renal function renal disease appears to be an important determinant of homocysteine concentrations in remote Aboriginal communities. The role of homocysteine concentrations as a potential mediator of the high rates of cardiovascular disease remains to be determined.

Topics: Adult; Albuminuria; Arteriosclerosis; Australia; Cardiovascular Diseases; Cross-Sectional Studies; Female; Folic Acid; Glomerular Filtration Rate; Homocysteine; Humans; Kidney Diseases; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Native Hawaiian or Other Pacific Islander; Polymorphism, Genetic; Regression Analysis; Rural Population; Vitamin B 12

Although moderate alcohol intake is associated with reduced risk of atherosclerotic disease in both the general population and in diabetic patients, a recent report suggests that heavy alcohol intake facilitates the development of atherosclerosis exclusively in diabetic individuals. We studied cross-sectionally the effects of the interaction between ethanol consumption category and the prevalence of diabetes on plasma total homocysteine (tHcy), a risk factor for atherosclerotic disease, in middle-aged men. Heavy drinking was associated with elevated tHcy levels only in diabetic subjects but not in non-diabetic subjects. Plasma tHcy of heavy drinkers (average ethanol consumption > 30 ml/day) was higher than that of abstainers in the diabetic subgroup (10.25 +/- 3.39 vs. 8.88 +/- 1.94 micromol/l, P < 0.05), whereas tHcy levels in heavy drinkers were comparable with that of abstainers in the non-diabetic subgroup (9.36 +/- 2.52 vs. 9.12 +/- 2.10 micromol/l, NS). In a two-factor anova, significant interaction was observed on the effects of ethanol consumption category and diabetes prevalence on tHcy levels (P < 0.01). Confounding factors including folate, vitamin B(12), creatinine, age or cigarette smoking did not contribute to the interaction. These findings may partly explain the reported association between heavy drinking and atherosclerosis in diabetic subjects.

Topics: Alcohol Drinking; Arteriosclerosis; Blood Glucose; Creatinine; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Folic Acid; gamma-Glutamyltransferase; Homocysteine; Humans; Male; Middle Aged; Prevalence; Risk Factors; Vitamin B 12

Black women have an increased risk of preeclampsia compared with white women. Plasma homocysteine is increased in preeclampsia. Homocysteine concentrations are affected by nutritional deficiencies, particularly decreased folic acid and B12, leading to increased homocysteine. Previous studies have reported racial differences in nutritional intake including folic acid. Therefore, we investigated whether there were racial differences in plasma homocysteine, folic acid, and vitamin B12 among women with preeclampsia. We tested for an association between homocysteine and folic acid and B12, and we hypothesized an inverse relationship of homocysteine and folic acid in preeclampsia, more so in black women in whom preeclampsia developed. Black women with preeclampsia (n=26) had elevated homocysteine concentrations (8.7+/-1.4 micromol/L) compared with black women with normal pregnancy (n=52, 7.6+/-0.5 micromol/L), white women with preeclampsia (n=34, 7.5+/-0.6 micromol/L), and white women with normal pregnancy (n=48, 5.5+/-0.3 micromol/L). Folic acid concentrations were lower in black women (14.1+/-0.8 ng/mL) compared with white women (18.5+/-0.9 ng/mL, P<0.01). However, plasma homocysteine was inversely related to folic acid only among black women with preeclampsia (r=-0.23, P=0.01). These racial differences may have implications for the higher rates of preeclampsia in this group and may have long-term implications for future cardiovascular risk. Racial differences in diet, adherence to folic acid supplementation, or interactions of nutritional and maternal factors warrant further study by race and pregnancy status.

Topics: Adolescent; Adult; Arteriosclerosis; Black People; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Maternal Age; Pennsylvania; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Risk Factors; Vitamin B 12; White People

Subclinical inflammation has been implicated in the initiation and/or progression of atherosclerosis. Diabetes mellitus and obesity are risk factors for atherosclerosis, and asymptomatic low grade inflammation occurs prior to overt vascular lesions in these patients. In contrast to adults, little information exists concerning low grade inflammation in young type 1 diabetes and juvenile obesity.. To investigate low grade inflammation and immune activation in juvenile diabetes mellitus and obesity.. hs-CRP, soluble interleukin-2 receptor (sIL-2R), C-peptide, insulin, cortisol, vitamin B12, folic acid, leptin, and homocysteine were determined in 148 patients with juvenile type 1 diabetes, 86 obese children and 142 normal weighted age-matched healthy controls. Intima-media thickness (IMT) and lumen diameter of both common carotid arteries (CCA) was measured by ultrasonography in 52 healthy pediatric controls, 10 diabetics, and 34 obese juveniles.. Serum hs-CRP was significantly elevated in patients with type 1 diabetes (p < 0.0001), and obese children (p < 0.0001) as compared to the control group. The obese juveniles (p < 0.0001) and the diabetics (p < 0.0001) showed significantly increased values for IMT of CAAs. Levels of homocysteine, sIL-2R, insulin, cortisol, vitamin B12, and folic acid did not differ from the controls. The elevation of hs-CRP was more pronounced in obesity as compared to type 1 diabetes (p < 0.0001), and the hs-CRP values correlated significantly with body mass index standard deviation score (BMI-SDS) values. Furthermore, the IMT and the luminal diameter of CCAs showed significant correlations with BMI-SDS values.. A low grade inflammation as determined by serum hs-CRP is significantly increased in children with type 1 diabetes, and even more pronounced in apparently healthy juveniles with obesity. The increased IMT of CCAs strongly argues for an association between this low grade inflammation and early atherosclerotic vessel injury.

Topics: Adolescent; Arteriosclerosis; Body Mass Index; C-Peptide; C-Reactive Protein; Carotid Artery, Common; Child; Diabetes Mellitus, Type 1; Female; Folic Acid; Homocysteine; Humans; Inflammation; Leptin; Male; Obesity; Receptors, Interleukin-2; Tunica Intima; Vitamin B 12

This study investigated in prepubertal obese children (POC), compared with prepubertal lean children (PLC), a possible relation among plasma total homocysteine (tHcy)-an independent risk factor for future atherosclerosis-and MCP-1 and RANTES, two circulating chemokines inducing leukocyte transendothelial migration (TEM), implicated in the initial stages of the inflammatory part of the atherosclerotic process. Seventy-two POC were evaluated for circulating tHcy, MCP-1, and RANTES, and compared with 42 healthy PLC. The mean adjusted (for age, sex as well as log10total insulin, vitB12, folate, total cholesterol, HDL cholesterol, log10triglycerides, and log10glucose levels) differences in tHcy, MCP-1, and RANTES levels between PLC and POC were all significant [1.16 nmol/mL (P = 0.03), 26.6 pg/mL (P = 0.02), and 52.9 pg/mL (P = 0.03), respectively]. In PLC, but not in POC, tHcy levels were negatively associated with both circulating MCP-1 (B = -1.68, P = 0.007) and RANTES (B = -1.16, P = 0.01) after adjusting for age, sex, BMI, as well as log10total insulin, vitB12, folate, total cholesterol, HDL cholesterol, log10triglycerides, and log10glucose levels. In conclusion, in POC there is a lack, in contrast to PLC, of a possibly autoregulatory, negative association of elevated tHcy levels to increased MCP-1 and RANTES levels. This could contribute to future, homocysteine-induced atherosclerosis.

Topics: Arteriosclerosis; Blood Glucose; Body Mass Index; Body Weight; Chemokine CCL2; Chemokine CCL5; Chemotaxis, Leukocyte; Child; Cholesterol, HDL; Data Interpretation, Statistical; Endothelium, Vascular; Female; Folic Acid; Homocysteine; Humans; Insulin; Male; Obesity; Puberty; Sex; Thinness; Triglycerides; Vitamin B 12

There is increasing evidence that plasma homocysteine level is an independent risk factor for atherosclerosis. Low levels of serum folates, cobalamin and pyridoxine are associated with increased risk of cardiovascular disease. Most dietary products contain cholesterol as well as methionine, so hyperlipidemia could be associated with a higher level of homocysteine and inversely with lower levels of B vitamins. The aim of this study was to investigate the differences in levels of lipids and vitamins affecting homocysteine metabolism in different groups of patients.. We examined 38 healthy persons, 55 patients hospitalised for cardiac surgery, and 62 patients without clinical evidence of atherosclerosis but with one of the atherosclerosis risk factors (hypercholesterolemia, NIDDM or chronic renal insufficiency). The levels of total cholesterol, triglycerides, vitamin B12, folic acid and vitamin B6 index in serum were determined using routine laboratory methods.. We found no association between lipids and B vitamins in any examined group. There were significant differences between concentrations of analysed parameters in all groups of patients as compared to controls.. The lack of correlation between the levels of lipid parameters and B vitamins in serum indicates that these may be independent, additional risk factors for atherosclerosis. Higher vitamin B6 deficiency in dialysis patients is probably caused by low intake combined with the increased requirements of uremic patients. Permanent monitoring of B vitamins in serum is necessary in patients with elevated risk of atherosclerosis, as well as long-term education, careful diet planning and supplementation.

Topics: Adult; Aged; Aged, 80 and over; Arteriosclerosis; Cardiac Surgical Procedures; Case-Control Studies; Cholesterol; Female; Folic Acid; Homocysteine; Humans; Hyperlipidemias; Lipids; Male; Middle Aged; Risk Factors; Triglycerides; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Topics: Adult; Age Factors; Aged; Arteriosclerosis; Clinical Trials as Topic; Dementia; Diet; Drug Therapy, Combination; Female; Folic Acid; Fruit; Homocysteine; Humans; Hyperhomocysteinemia; Male; Myocardial Infarction; Prospective Studies; Risk Factors; Sex Factors; Stroke; Vegetables; Vitamin B 12; Vitamin B 6

Hyperhomocysteinemia may constitute an independent risk factor for cardiovascular disease and may promote atherothrombosis. Psoriasis is one of the diseases associated with increased atherothrombosis. The aim of the present study was to examine serum total homocysteine (tHcy) level and its relationships with atherothrombotic markers.. The study group included 30 patients with psoriasis (17 females and 13 males) with a mean age of 34.2 (age range: 27-40) and 30 sex and age matched healthy volunteers (15 females and 15 males) with a mean age of 36.7 (age range: 26-48). The concentrations of lipids, lipoproteins, acute phase reactants, tHcy and atherothrombotic markers [fibronectin, soluble vascular adhesion molecules-1 (sVCAM-1), soluble intercellular adhesion molecules-1 (sICAM-1), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), autoantibodies against oxidized LDL (AuAb-oxLDL)] were determined.. The mean levels of serum tHcy, fibrinogen, fibronectin, sICAM, PAI-1 and AuAb-oxLDL were increased in patients whereas tPA, vitamin B(12) and folate levels were decreased significantly. Increased levels of sVCAM were not statistically significant. tHcy levels were negatively correlated with vitamin B(12) (r=-0.40, P=0.027) and positively correlated with PAI-1 and AuAb-oxLDL levels (r=0.46, P=0.011; r=0.39, P=0.035, respectively).. It was concluded that the increased homocysteine concentration and altered endothelial cell-mediated proteins associated with increased lipids and LDL oxidation may play an important role for the development of atherothrombotic complications with psoriasis.

Topics: Acute-Phase Proteins; Adult; Arteriosclerosis; Autoantibodies; Biomarkers; Female; Fibrinogen; Fibronectins; Folic Acid; Homocysteine; Humans; Lipoproteins, LDL; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Psoriasis; Thrombosis; Tissue Plasminogen Activator; Vitamin B 12

Topics: Arteriosclerosis; Cardiovascular Diseases; Clinical Trials as Topic; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Vitamin B 12

Weak hyperhomocysteinemia is a risk factor for the development of atherothrombotic vascular complication. Their plasma levels are affected by nutritional and pharmacologic factors, tobacco, certain metabolic state and gender. In HIV+ patients, the wasting syndrome or chronic diarrheas could affect the levels of homocysteine (Hcy), as well as some adverse effects of the new antiretroviral therapies (lipodystrophy syndrome: insulin resistance and/or dislypemia). The levels of Hcy were evaluated in 53 HIV+ patients without any treatment and in 75 HIV+ under treatment with and without metabolic disturbances (n = 43; n = 32, respectively).. 32 HIV negative individuals. We looked for association with folic acid, vitamin B12, lipids, insulin resistance status, activation platelets (soluble P-selectin) and endothelial injury (soluble trombomodulin) markers; and also their relation with tobacco, disease status and kind of treatment. There were no statistically significant differences in the mean levels of vitamin B12, Hcy, P-selectin and insulin resistance status between the control group and the HIV+; 16.4% of the 128 HIV+ patients had Hcy > or = 15 mumol/L and the control group had 12.9% (p = 0.617). The levels of Hcy correlated with the levels of folic acid (Rho = -0.314, p < 0.01) and age (Rho = 0.277, p < 0.01) among HIV+. There were no statistically significant differences in the levels of Hcy neither between smokers and non smokers (p = 0.452) nor between HIV+ AIDS or HIV+ no AIDS (p = 0.774) nor with the use of certain antiretrovirals (p = 0.801). The hyperhomocysteinemia (a well known atherothrombotic risk factor) is not frequently associated with HIV infected patients. The levels of Hcy would not seem to be influenced either by the HIV condition or by the antiretroviral treatments or their adverse effects.

Topics: Adult; Anti-HIV Agents; Arteriosclerosis; Biomarkers; Case-Control Studies; Female; Folic Acid; HIV Infections; Homocysteine; Humans; Hyperhomocysteinemia; Insulin Resistance; Male; P-Selectin; Risk Factors; Smoking; Vitamin B 12

Methionine is the precursor of homocysteine, a sulfur amino acid intermediate in the methylation and transsulfuration pathways. Elevated plasma homocysteine (hyperhomocysteinemia) is associated with occlusive vascular disease. Whether homocysteine per se or a coincident metabolic abnormality causes vascular disease is still an open question. Animals with genetic hyperhomocysteinemia have so far not displayed atheromatous lesions. However, when methionine-rich diets are used to induce hyperhomocysteinemia, vascular pathology is often observed. Such studies have not distinguished the effects of excess dietary methionine from those of hyperhomocysteinemia. We fed apolipoprotein E-deficient mice with experimental diets designed to achieve three conditions: (i) high methionine intake with normal blood homocysteine; (ii) high methionine intake with B vitamin deficiency and hyperhomocysteinemia; and (iii) normal methionine intake with B vitamin deficiency and hyperhomocysteinemia. Mice fed methionine-rich diets had significant atheromatous pathology in the aortic arch even with normal plasma homocysteine levels, whereas mice fed B vitamin-deficient diets developed severe hyperhomocysteinemia without any increase in vascular pathology. Our findings suggest that moderate increases in methionine intake are atherogenic in susceptible mice. Although homocysteine may contribute to the effect of methionine, high plasma homocysteine was not independently atherogenic in this model. Some product of excess methionine metabolism rather than high plasma homocysteine per se may underlie the association of homocysteine with vascular disease.

Topics: Animals; Aorta; Apolipoproteins E; Arteriosclerosis; Diet; Homocysteine; Hyperhomocysteinemia; Male; Methionine; Mice; Models, Biological; Vitamin B 12; Vitamin B 6; Vitamin B Deficiency

Topics: Adult; Arteriosclerosis; Aspirin; C-Reactive Protein; Case-Control Studies; Contraceptives, Oral; Female; Fibrinogen; Folic Acid; Humans; Hyperhomocysteinemia; Inflammation; Male; Meta-Analysis as Topic; Migraine Disorders; Risk Factors; Smoking; Stroke; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator; Vitamin B 12; Vitamin B 6

High plasma homocysteine, a risk factor for atherosclerosis, is frequently caused by a common mutation in the gene for the enzyme, 5,10-methylenetetrahydrofolate reductase (MTHFR), C677T (alanine to valine substitution) or low intake of B vitamins that affect the remethylation or transsulfuration pathways in homocysteine metabolism. However, the interaction of the C677T mutation and B vitamins other than folate has not been well elucidated. We conducted a cross-sectional survey of 324 men and 641 women who participated in a 1996 health examination under a hypothesis that high nutritional status of folate, vitamin B12 and vitamin B6 expressed as high serum levels, may compensate for the hyperhomocysteinemia associated with homozygosity for the C677T mutation, but not for having the mutation per se. Age-adjusted plasma homocysteine levels were higher for both men and women with the homozygous genotype for the mutation than those who were heterozygous or had no mutation. Elevated homocysteine levels in homozygous genotype was attenuated among persons with higher serum levels of vitamin B12 and folate, but not vitamin B6, and among persons with the combination of lower folate and higher vitamin B12 and of higher folate and higher vitamin B12, split by the median. These findings suggest that elevated homocysteine levels among Japanese with the homozygous genotype for the MTHFR gene mutation can be modified efficiently by dietary supplement of vitamin B12 as well as folate.

Topics: Adult; Age Distribution; Aged; Arteriosclerosis; Cross-Sectional Studies; Data Collection; Female; Folic Acid; Genotype; Homocysteine; Humans; Incidence; Japan; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Probability; Reference Values; Risk Assessment; Sampling Studies; Sensitivity and Specificity; Sex Distribution; Vitamin B 12; Vitamin B 6

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Arteriosclerosis; Cardiovascular Diseases; Chlamydia Infections; Controlled Clinical Trials as Topic; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Folic Acid; Humans; Hypercholesterolemia; Hyperhomocysteinemia; Hypertension; Hypolipidemic Agents; Infections; Male; Middle Aged; Multicenter Studies as Topic; Obesity; Randomized Controlled Trials as Topic; Risk Factors; Vitamin B 12; Vitamin B Complex

Thioretinamide was conjugated to coenzyme B12 to produce thioretinaco. Thioretinamide, thioretinaco, and coenzyme B12 were injected weekly into Rattus rattus that were also given atherogenic doses of homocysteine thiolactone. The presence or absence of lesions in aorta-intercostal artery junctions was examined. Control rats injected with homocysteine thiolactone (CON-Hcy) had 56.6 +/- 5.8% lesions when compared to 34.8 +/- 3.4% in control rats injected with saline (CON-Sal). Rats that received homocysteine thiolactone injection with thioretinamide (NHTR-Hcy), thioretinaco ((NHTR)2B12-Hcy), and coenzyme B12 (B12-Hcy) had 30.1 +/- 4.2%, 27.5 +/- 3.5%, and 22.8 +/- 3.0% lesions, respectively. These lesion rates were not different from those of rats receiving thioretinamide (NHTR-Sal), thioretinaco ((NHTR)2B12-Sal), and coenzyme B12 (B12-Sal) which were 31.3 +/- 1.8%, 29.8 +/- 3.9%, and 32.0 +/- 4.6%, respectively. In this study the percentage of intercostal artery lesions in rats receiving thioretinamide and homocysteine (NHTR-Hcy), coenzyme B12 and homocysteine (B12-Hcy), and thioretinaco and homocysteine ((NHTR)2/B12-Hcy) were significantly lower, 53.2%, 48.6%, and 40.3% respectively, compared to than that of the control group receiving homocysteine (CON-Hcy). Thioretinaco, thioretinamide, and coenzyme B12 provided protective effects against the atherogen homocysteine thiolactone. A new method for the synthesis of the N-substituted derivative of homocysteine thiolactone, thioretinamide, was also reported.

Topics: Animals; Aorta, Thoracic; Arterial Occlusive Diseases; Arteries; Arteriosclerosis; Cobamides; Female; Food; Homocysteine; Magnetic Resonance Spectroscopy; Mass Spectrometry; Propylene Glycol; Rats; Tissue Fixation; Tretinoin; Vitamin B 12; Weight Gain

Topics: Adult; Aged; Alzheimer Disease; Arteriosclerosis; Brain; Cerebral Infarction; Folic Acid; Humans; Hyperhomocysteinemia; Male; Risk Factors; Stroke; Vitamin B 12

Hyperhomocysteinemia is associated with increased risk of atherosclerotic and thrombotic vascular disease. In many patients, hyperhomocysteinemia can be treated or prevented by dietary supplementation with B vitamins, but the clinical benefit of B vitamins for the prevention of vascular disease has not been proven.. Using an atherogenic diet that produces both hyperhomocysteinemia and hypercholesterolemia, we tested the hypothesis that dietary supplementation with B vitamins (folic acid, vitamin B(12), and vitamin B(6)) would prevent hyperhomocysteinemia, vascular dysfunction, and atherosclerotic lesions in monkeys. After 17 months, plasma total homocysteine increased from 3.6+/-0.3 to 11.8+/-1.7 micromol/L in monkeys fed an unsupplemented atherogenic diet (P<0.01) but did not increase in monkeys fed an atherogenic diet supplemented with B vitamins (3.8+/-0.3 micromol/L). Serum cholesterol increased from 122+/-7 to 550+/-59 mg/dL in the unsupplemented group (P<0.001) and from 118+/-5 to 492+/-55 mg/dL in the supplemented group (P<0.001). Responses to endothelium-dependent vasodilators, both in resistance vessels in vivo and in the carotid artery ex vivo, were impaired to a similar extent in groups that did and did not receive vitamin supplements. Anticoagulant responses to the infusion of thrombin were also impaired to a similar extent in both groups. Vitamin supplementation failed to prevent intimal thickening in the carotid or iliac arteries.. These findings demonstrate that supplementation with B vitamins prevents hyperhomocysteinemia but is not sufficient to prevent the development of vascular dysfunction or atherosclerotic lesions in monkeys with marked hypercholesterolemia, even in the absence of preexisting atherosclerosis.

Topics: Animals; Arteriosclerosis; Blood Coagulation; Carotid Arteries; Cholesterol; Diet, Atherogenic; Dietary Supplements; Disease Models, Animal; Folic Acid; Hypercholesterolemia; Hyperhomocysteinemia; In Vitro Techniques; Macaca fascicularis; Partial Thromboplastin Time; Pyridoxine; Thrombin; Treatment Outcome; Vascular Diseases; Vasodilation; Vasodilator Agents; Vitamin B 12

Although hyperhomocysteinemia (HHcy) is a well-known risk factor for the development of cardiovascular disease, the underlying molecular mechanisms are not fully elucidated. Here we show that induction of HHcy in apoE-null mice by a diet enriched in methionine but depleted in folate and vitamins B6 and B12 increased atherosclerotic lesion area and complexity, and enhanced expression of receptor for advanced glycation end products (RAGE), VCAM-1, tissue factor, and MMP-9 in the vasculature. These homocysteine-mediated (HC-mediated) effects were significantly suppressed, in parallel with decreased levels of plasma HC, upon dietary supplementation with folate and vitamins B6/B12. These findings implicate HHcy in atherosclerotic plaque progression and stability, and they suggest that dietary enrichment in vitamins essential for the metabolism of HC may impart protective effects in the vasculature.

Topics: Animals; Apolipoproteins E; Arteriosclerosis; Cells, Cultured; Diet; Disease Models, Animal; Folic Acid; Humans; Hyperhomocysteinemia; Immunohistochemistry; Male; Matrix Metalloproteinase 9; Methionine; Mice; Mice, Inbred C57BL; Mice, Knockout; Pyridoxine; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Thromboplastin; Vascular Cell Adhesion Molecule-1; Vasculitis; Vitamin B 12

Topics: Arteriosclerosis; Biomarkers; Endothelium, Vascular; Homocysteine; Humans; Pyridoxine; Risk Factors; Vitamin B 12

Hyperhomocysteinemia is a risk factor for atherosclerosis that is common in chronic renal failure (CRF), but its cause is unknown. Homocysteine metabolism is linked to betaine-homocysteine methyl transferase (BHMT), a zinc metalloenzyme that converts glycine betaine (GB) to N,N dimethylglycine (DMG). DMG is a known feedback inhibitor of BHMT. We postulated that DMG might accumulate in CRF and contribute to hyperhomocysteinemia by inhibiting BHMT activity.. Plasma and urine concentrations of GB and DMG were measured in 33 dialysis patients (15 continuous ambulatory peritoneal dialysis and 18 hemodialysis), 33 patients with CRF, and 33 age-matched controls. Concentrations of fasting plasma total homocysteine (tHcy), red cell and serum folate, vitamins B(6) and B(12), serum zinc, and routine biochemistry were also measured. Groups were compared, and determinants of plasma tHcy were identified by correlations and stepwise linear regression.. Plasma DMG increased as renal function declined and was twofold to threefold elevated in dialysis patients. Plasma GB did not differ between groups. The fractional excretion of GB (FE(GB)) was increased tenfold, and FED(MG) was doubled in CRF patients compared with controls. Plasma tHcy correlated positively with plasma DMG, the plasma DMG:GB ratio, plasma creatinine, and FE(GB) and negatively with serum folate, zinc, and plasma GB. In the multiple regression model, only plasma creatinine, plasma DMG, or the DMG:GB ratio was independent predictors of tHcy.. DMG accumulates in CRF and independently predicts plasma tHcy concentrations. These findings suggest that reduced BHMT activity is important in the pathogenesis of hyperhomocysteinemia in CRF.

Topics: Adult; Aged; Aged, 80 and over; Arteriosclerosis; Betaine; Betaine-Homocysteine S-Methyltransferase; Creatinine; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methyltransferases; Middle Aged; Peritoneal Dialysis; Predictive Value of Tests; Pyridoxine; Renal Dialysis; Sarcosine; Uremia; Vitamin B 12; Zinc

Hyperhomocysteinemia is an independent risk factor for vascular disease, frequently observed in patients with severe renal impairment. Hyperhomocysteinemia has never been considered as a possible risk factor in renal artery stenosis. We investigated plasma folate and vitamin B12, methylenetetrahydrofolate reductase (MTHFR) C677T and cystathionine beta-synthase (CBS) 844ins68 polymorphisms, and homocysteine levels before and after methionine (100 mg/kg) loading in 58 patients with angiographically documented renal artery stenosis and mildly impaired renal function. One hundred and two normotensive subjects with angiographically normal coronary arteries and no history or clinical or angiographic evidence of atherosclerosis in other vascular districts, were considered as a control group. Mean total homocysteine levels were significantly higher in patients than in controls (P<0.01), as was the prevalence of hyperhomocysteinemia (51.7% vs. 32.3%, P<0.05). However, MTHFR alleles and genotypes as well as CBS 844ins68 mutation frequencies were similar in the two groups, whereas a lower folate level was observed in the patients. Moreover, patients with MTHFR A/A genotype showed a poorer folate status than control subjects, suggesting that a subclinical folate deficiency may be very frequent in renal artery stenosis, regardless of C677T mutation. In conclusions, hyperhomocysteinemia is common in patients with atheromatous renal artery stenosis; a subclinical folate deficiency seems to be involved, regardless of MTHFR thermolabile or CBS insertion genotypes. Folate supplementation might be useful in the management of overall vascular risk of these patients.

Topics: Aged; Alleles; Arteriosclerosis; Case-Control Studies; Cystathionine beta-Synthase; Female; Folic Acid; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Renal Artery Obstruction; Risk Factors; Vitamin B 12

Mild hyperhomocysteinemia has been considered a cardiovascular risk factor. However, recent prospective studies have not demonstrated that hyperhomocysteinemia or the underlying genetic defect on methylentetrahydrofolate reductase is associated with a higher risk of coronary or peripheral artery disease. We compared serum homocysteine, folate, and vitamin B(12) levels of patients with coronary and peripheral vascular disease with those of age- and sex-matched healthy individuals. Subjects taking multivitamins, with diabetes mellitus, or serum creatinine levels over 1.5 mg/dL were excluded from the study. Homocysteine was measured by fluorimetric high-performance liquid chromatography. Serum folate and vitamin B(12) levels were measured by an ion-capture method. We studied 32 patients with peripheral vascular disease (10 female), aged 69.6 +/- 11 y, 24 age- and sex-matched control subjects, 52 patients with coronary artery disease (7 female), aged 59.5 +/- 10.4 y, and 42 age- and sex-matched control subjects. Serum homocysteine levels were 11.7 +/- 7.4 and 9.3 +/- 4.5 micromol/L in vascular patients and in the control counterparts, respectively (not significant). The levels for coronary patients and the control counterparts were 9.0 +/- 3.9 and 8.6 +/- 3.6 micromol/L, respectively (not significant). Folate levels were 4.48 +/- 2.42 and 7.14 +/- 4.04 ng/mL in vascular patients and control subjects, respectively (P < 0.02); the levels in coronary patients and control counterparts were 5.15 +/- 1.9 and 6.59 +/- 2.49 ng/mL, respectively (P < 0.01). No differences in vitamin B(12) or tocopherol levels were observed between patients and control subjects. There were no differences in homocysteine levels, but lower serum folate levels were observed when comparing patients with atherosclerotic vascular disease and healthy control subjects.

Topics: Aged; Arteriosclerosis; Cholesterol; Chromatography, High Pressure Liquid; Coronary Disease; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Lipoproteins, HDL; Male; Middle Aged; Risk Factors; Triglycerides; Vitamin B 12; Vitamin E

Hyperhomocysteinemia has been increasingly recognized as an important risk factor for elevated atherosclerotic vascular disease in chronic renal failure. We measured in patients with chronic renal failure homocysteine and metabolites of its 2 metabolic pathways, transulfuration (cystathionine, cysteine) and remethylation (methionine, methylmalonic acid, 2-methylcitric acid).. Eleven patients on conservative treatment (creatinine clearance 10 to 30 ml/min) and 50 chronic uremic subjects on regular hemodialysis were included in the study. Twenty-two of the dialysis patients received daily oral multivitamin supplementation containing 10 mg vitamin B6, 6 micrograms vitamin B12, and 1 mg folic acid during the last year before the study started.. In the hemodialysis group homocysteine levels were higher compared with the patients on conservative treatment. Hemodialysis patients with additional vitamin supplementation showed significantly lower homocysteine levels than those without. The pattern of metabolites was different to these results: all metabolites were higher in hemodialysis patients, too (significant for cysteine and methionine), but vitamin supplementation failed to lower all metabolites.. Analysis of metabolites additional to homocysteine levels may help to understand different results in evaluation of atherosclerotic risk of hyperhomocysteinemia in chronic renal failure.

Topics: Adult; Aged; Arteriosclerosis; Cysteine; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methionine; Middle Aged; Pyridoxine; Renal Dialysis; Severity of Illness Index; Vitamin B 12; Vitamin B Complex

Plasma homocysteine level is a risk factor for coronary events, stroke, and peripheral atherosclerotic disease. However, few data are available concerning the relationship between homocysteine level and severity of thoracic aortic atherosclerosis. We hypothesized in this multiplane transesophageal echocardiography (TEE) study that homocysteine level is a marker of the presence and severity of thoracic aortic atherosclerosis.. Cross-sectional study.. University hospital.. Risk factors, angiographic features, and TEE findings were analyzed prospectively in 82 valvular patients.. The following risk factors were recorded: age, gender, hypertension, smoking, lipid parameters, diabetes, body mass index, and family history of coronary artery disease. Plasma levels of homocysteine, vitamin B(12), and folic acid were measured for each patient. By univariate analysis, age, diabetes, hypertension, smoking, family history of coronary artery disease, and levels of homocysteine, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were significant predictors of the presence of thoracic aortic plaques. There was a positive correlation between the plasma homocysteine levels and the score of severity of thoracic atherosclerosis (r = 0.48; p = 0.0001) as well as between the homocysteine levels and the grades of severity of aortic intimal changes (p = 0.0008). Multivariate regression analysis revealed that homocysteine was an independent predictor of the presence and severity of thoracic aortic atherosclerosis.. This prospective study indicates that plasma homocysteine level is a marker of severity of thoracic atherosclerosis detected by multiplane TEE. These findings emphasize the role of homocysteine as a marker of atherosclerotic lesions in the major arterial locations.

Topics: Adult; Aged; Aged, 80 and over; Aorta, Thoracic; Aortic Diseases; Arteriosclerosis; Biomarkers; Cholesterol; Coronary Artery Disease; Cross-Sectional Studies; Echocardiography, Transesophageal; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Risk Factors; Vitamin B 12

Values of homocysteine and lipid parameters were measured in groups of adults consuming alternative nutrition (vegetarians/lactoovo/, vegans) and compared with a group consuming traditional diet (omnivores, general population). Frequency of hyperhomocysteinemia was 53% in the vegans group, 28% in vegetarians vs. 5% in omnivores. In conditions of lower methionine intake (reduced content in plant proteins), the remethylation pathway of homocysteine metabolism prevails and it is vitamin B12 and folate-dependent. The intake of vitamin B12 is equal to zero in vegans; vegetarians consume 124% of the RDA vs. 383% in omnivores. Serum vitamin levels are significantly lower in subjects consuming alternative nutrition with deficiency observed in 24% of vegetarians, 78% of vegans vs. 0% in omnivores. Serum folate levels are within the reference range in all groups. Mild hyperhomocysteinemia in the groups consuming alternative diet is a consequence of vitamin B12 deficiency. Vegetarians and vegans meet the RDA for energy and fat, and have a favourable proportion of saturated, mono- and polyunsaturated fatty acids on total energy intake; the ratio of linoleic/alpha-linolenic acid in their diet corresponds with the recommendations. They have low cholesterol consumption and higher vitamin E and C intake. Optimal fat intake of correct composition is reflected in lower values of atherosclerosis risk factors (cholesterol, LDL-cholesterol, atherogenic index, saturated fatty acids, triacylglycerols), and significantly higher levels of protective substances (linoleic acid, alpha-linolenic acid, HDL-cholesterol, vitamin E, vitamin E/cholesterol, vitamin C). Low lipid risk factors but higher findings of mild hyperhomocysteinemia in vegetarians mean a diminished protective effect of alternative nutrition in cardiovascular disease prevention.

Topics: Adult; Aged; Arteriosclerosis; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dairy Products; Diet, Vegetarian; Eggs; Female; Folic Acid; Homocysteine; Humans; Lipids; Male; Methionine; Middle Aged; Nutritional Physiological Phenomena; Reference Values; Risk Factors; Vitamin B 12

Hyperhomocysteinemia has been identified as a potential risk factor for atherosclerosis. This study examined whether a modest elevation of plasma total homocysteine (tHcy) was an independent risk factor for increased carotid artery intimal-medial wall thickness (IMT) and focal plaque formation in a large, randomly selected community population. We also examined whether vitamin cofactors and the C677T genetic mutation of the methylenetetrahydrofolate reductase (MTHFR) enzyme were major contributors to elevated plasma tHcy and carotid vascular disease.. In 1111 subjects (558 men, 553 women) 52+/-13 years old (mean+/-SD; range, 27 to 77 years) recruited from a random electoral roll survey, we measured fasting tHcy and performed bilateral carotid B-mode ultrasound. For the total population, mean tHcy was 12.1+/-4.0 micromol/L. Plasma tHcy levels were correlated with IMT (Spearman rank rs=0.31, P=0.0001). After adjustment for age, sex, and other conventional risk factors, subjects in the highest versus the lowest quartile of tHcy had an odds ratio of 2.60 (95% CI, 1.51 to 4.45) for increased IMT and 1.76 (95% CI, 1.10 to 2.82) for plaque. Serum and dietary folate levels and the C677T mutation in MTHFR were independent determinants of tHcy (all P=0.0001). The mutant homozygotes (10% of the population) had higher mean tHcy than heterozygotes or those without the mutation (14.2 versus 12.3 versus 11.6 micromol/L, respectively, P=0.0001). The inverse association of folate levels with tHcy was steeper in the mutant homozygotes. Despite this, the C677T MTHFR mutation was not independently predictive of increased carotid IMT or plaque formation.. Mild hyperhomocysteinemia is an independent risk factor for increased carotid artery wall thickness and plaque formation in a general population. Lower levels of dietary folate intake and the C677T mutation in MTHFR are important causes of mild hyperhomocysteinemia and may therefore contribute to vascular disease in the community.

Topics: Adult; Aged; Amino Acid Substitution; Arteriosclerosis; Carotid Arteries; Carotid Stenosis; Comorbidity; Diet; Female; Folic Acid; Gene Frequency; Genetic Predisposition to Disease; Genotype; Health Surveys; Homocysteine; Humans; Hyperhomocysteinemia; Hyperlipidemias; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation, Missense; Obesity; Odds Ratio; Oxidoreductases Acting on CH-NH Group Donors; Point Mutation; Pyridoxine; Risk Factors; Smoking; Tunica Intima; Ultrasonography; Vitamin B 12; Western Australia

Elevated plasma total homocysteine (tHcy) levels, either measured in the fasting state or after oral methionine loading, are associated with an increased risk of atherothrombotic disease. Fasting and post-methionine hyperhomocysteinemia (HHC) overlap to a limited extent; both can occur as familial traits. We investigated determinants of fasting, postmethionine and delta (ie, post-methionine minus fasting levels) tHcy levels in 510 subjects of 192 HHC-prone families including 161 patients with clinical vascular disease and 349 without vascular disease. We focused on tHcy levels in relation to levels of vitamin B12, B6 and folate and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Multivariate linear analyses adjusted for the presence of vascular disease showed that fasting tHcy was significantly related to folate and vitamin B12, and the presence of the MTHFR TT genotype and the T allele, and to age, smoking habits, and serum levels of creatinine. Both post-methionine and delta tHcy levels were related to serum folate levels, and the presence of the MTHFR TT genotype and the T allele, and to postmenopausal status, and body mass index. An interaction was found between MTHFR TT genotype and serum folate levels for both fasting and post-methionine tHcy, ie, for a given decrease in serum folate, homocysteine levels increased more in subjects with the TT genotype than in those with the CC genotype. Fasting, post-methionine and delta tHcy were higher in patients with vascular disease than in their healthy siblings, but these levels were less dependent on serum folate levels (P<0.05), whereas the effect of MTHFR genotype was stronger (P=0.01). This study found evidence that post-methionine and delta tHcy levels are not only influenced by factors affecting homocysteine transsulfuration but also by factors that affect remethylation. The explained variances of fasting, post-methionine and delta tHcy were 49%, 62%, and 78%, respectively. We also found evidence, in patients with premature vascular disease but not in their healthy siblings, for a factor that increases tHcy levels but weakens the normal inverse relation between folate and tHcy and amplifies the effect of the MTHFR genotype.

Topics: Adult; Age Factors; Amino Acid Substitution; Arteriosclerosis; Body Mass Index; Comorbidity; Fasting; Female; Folic Acid; Genetic Predisposition to Disease; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Hypertension; Lipids; Male; Menopause; Methionine; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Pyridoxine; Smoking; Vitamin B 12

Blood homocyst(e)ine levels are an important, independent and frequent risk factor for clinical atherosclerosis and venous thrombosis. Folic acid, vitamins B6 and B12, renal and thyroid functions, certain medications and certain genotypes are known to modulate plasma homocyst(e)ine levels. Intake of B vitamins through diet, supplementation and fortified foods effectively reduces homocyst(e)ine concentration and thus may reduce the risk of cardiovascular disease. This is true even in individuals who are genetically predisposed to hyperhomocyst(e)inemia. Randomized clinical trials are needed to investigate these effects further.

Topics: Arteriosclerosis; Female; Genotype; Homocysteine; Humans; Male; Middle Aged; Pyridoxine; Risk Factors; Thrombophlebitis; Vitamin B 12

Hyperhomocyst(e)inemia is now recognized as an independent risk factor for atherosclerotic cardiovascular disease in patients with normal renal function. Hyperhomocyst(e)inemia is common in patients with chronic renal failure. This study is designed to look for an association between hyperhomocyst(e)inemia and atherosclerotic vascular disease in patients with end-stage renal disease (ESRD). Two hundred eighteen patients undergoing hemodialysis were enrolled onto the study and had predialysis bloodwork performed for total homocyst(e)ine, red blood cell folate, and vitamin B(12) levels. A history of clinically significant atherosclerotic vascular disease (ischemic heart disease, cerebrovascular disease, or peripheral vascular disease) was elicited by patient questionnaire and verified by careful inpatient and outpatient chart review. Atherosclerotic vascular disease was present in 45.9% of patients. Mean homocyst(e)ine concentration was 26.7 micromol/L (95% confidence interval [CI], 25.0 to 28.4) overall. Mean homocyst(e)ine concentration was 28.6 micromol/L (95% CI, 25.6 to 31.7) and 25.0 micromol/L (95% CI, 23.2 to 26.8) in patients with and without atherosclerotic disease, respectively (P = 0.036). The adjusted odds ratio for atherosclerotic disease was 2.12 (95% CI, 1.03 to 4.39) for those subjects with a homocyst(e)ine level in the highest quartile compared with the lowest 3 quartiles. In the 126 men, the adjusted odds ratio for atherosclerotic disease was 3.4 (95% CI, 1. 24 to 9.42) for those with homocyst(e)ine levels in the highest quartile compared with the lowest 3 quartiles. No association was found between homocyst(e)ine level and atherosclerotic disease in women. In conclusion, there is an association between hyperhomocyst(e)inemia and atherosclerotic vascular disease in patients undergoing dialysis. Prospective studies need to further examine the relationship between homocyst(e)ine level and atherosclerosis in women with ESRD.

Topics: Aged; Arteriosclerosis; Coronary Artery Disease; Cross-Sectional Studies; Erythrocytes; Female; Folic Acid; Homocysteine; Homocystine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Middle Aged; Odds Ratio; Renal Dialysis; Retrospective Studies; Risk Factors; Sex Factors; Vitamin B 12

Mild hyperhomocyst(e)inaemia is a risk factor for atherosclerotic vascular disease. In-vitro studies have shown that autooxidation of homocyst(e)ine is accompanied by the generation of oxygen radicals. This may lead to oxidative modification of low-density lipoproteins (LDL) and promote atherosclerotic vascular lesions. In male patients with peripheral arterial occlusive disease we determined fasting and post methionine load homocyst(e)ine levels by high performance liquid chromatography and the susceptibility of their LDL particles to ex-vivo oxidation by continously measuring the conjugated diene production induced by incubation with copper ions. Oxidation resistance (expressed as lag time), maximal oxidation rate, and extent of oxidation (expressed of total diene production) of LDL from patients with normal or mildly elevated homocyst(e)ine levels did not differ significantly. Folic acid, pyridoxal phosphate and cobalamin supplementation significantly decreased plasma homocyst(e)ine levels in hyperhomocyst(e)inaemic patients. This went along with a significant decrease in the extent of LDL oxidation and additionally increased HDL-cholesterol levels. The clinical relevance of these findings for the long-term course of atherosclerotic vascular disorders has to be determined by intervention studies.

Topics: Adult; Aged; Arteriosclerosis; Folic Acid; Homocysteine; Humans; Hypercholesterolemia; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction; Peripheral Vascular Diseases; Pyridoxal Phosphate; Risk Factors; Vitamin B 12

Homocysteine (HC) at concentrations of from 0.05 to 1.0 mM caused dose-dependent loss of [Mg2+]i in cultured cerebral vascular smooth muscle cells (VSMC), whereas cysteine and methionine (its metabolic products) failed to interfere with changes in [Mg2+]i. HC, methionine and cysteine did not produce any changes in [Ca2+]i. Lowering [Mg2+]o to 0.3 mM resulted in elevation of [Ca2+]i and loss of [Mg2+]i. Depletion of [Mg2+]i, induced by HC, was potentiated by low Mg2+. Preincubation of these cells with vitamin B6, vitamin B12, folic acid, alone, did not alter [Ca2+]i or [Mg2+]i. Likewise, concomitant addition of vitamin B6, vitamin B12, or folic acid, together with HC (1 mM) did not change the reduction in [Mg2+]i induced by HC. However, concomitant addition of HC and the three vitamins inhibited completely the loss of [Mg2+]i. Exposure of these cells to each vitamin, alone, or combination of the three vitamins failed to interfere with reduction in [Mg2+]i induced by low [Mg2+]i, but it did suppress the rise in [Ca2+]i. Interestingly, in the presence of low [Mg2+]o, the vitamin combination did not retard depletion of [Mg2+]i. The present findings are compatible with the hypothesis that an increased serum HC concentration causes abnormal metabolism of Mg2+ in cerebral VSMC, thus priming these cells for HC-induced atherogenesis, cerebral vasospasm and stroke. Our results suggest the need for the three B-vitamins, together with normal physiological levels of Mg2+, in order to prevent [Mg2+]i depletion and occlusive cerebral vascular diseases induced by homocysteinemia.

Topics: Animals; Arteriosclerosis; Basilar Artery; Calcium; Cells, Cultured; Cerebral Arteries; Dogs; Folic Acid; Homocysteine; Hyperhomocysteinemia; Magnesium; Microscopy, Fluorescence; Muscle, Smooth, Vascular; Pyridoxine; Signal Transduction; Stroke; Vitamin B 12; Vitamins

Atherosclerosis of the vascular system has classically been attributed to elevated serum cholesterol concentrations. Recently, it has been found that reduced serum levels of folic acid, vitamin B12, and vitamin B6 are related to the etiology of atherosclerosis and coronary heart disease. These deficiencies lead to inadequate production of S-adenosyl-methionine, creating a condition of hypomethylation. It is hypothesized that this causes hypomethylation of the DNA in cells in the arterial intima resulting in mutation and proliferation of smooth-muscle cells which lead to the formation of atheroma. It is further hypothesized that such action can be reversed by supraphysiological doses of these three vitamins to reduce or remove existing atheroma. It is recommended that all patients suffering from atherosclerosis and having deficiencies of any of these three vitamins and/or an elevation of serum homocysteine receive supplementation to prevent worsening of their condition.

Topics: Arteriosclerosis; DNA Methylation; Folic Acid; Homocysteine; Humans; Models, Biological; Mutation; Vitamin B 12

We found a higher plasma concentration of total homocysteine (tHcy), an independent risk factor for cardiovascular disease, in patients with hypothyroidism (mean, 16.3 micromol/L; 95% confidence interval [CI], 14.7 to 17.9 micromol/L) than in healthy controls (mean, 10.5 micromol/L; 95% CI, 10.1 to 10.9 micromol/L). The tHcy level of hyperthyroid patients did not differ significantly from that of the controls. Serum creatinine was higher in hypothyroid patients and lower in hyperthyroid patients than in controls, whereas serum folate was higher in hyperthyroid patients compared with the two other groups. In multivariate analysis, these differences did not explain the higher tHcy concentration in hypothyroidism. We confirmed the observation of elevated serum cholesterol in hypothyroidism, which together with the hyperhomocysteinemia may contribute to an accelerated atherogenesis in these patients.

Topics: Adult; Aged; Arteriosclerosis; Cardiovascular Diseases; Cholesterol; Creatinine; Female; Folic Acid; Homocysteine; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Multivariate Analysis; Risk Factors; Thyroxine; Triiodothyronine; Vitamin B 12

Topics: Aged; Arteriosclerosis; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Pyridoxine; Vitamin B 12; Vitamins

Studies have demonstrated that hyperhomocyst(e)inemia is present in renal transplant recipients and is correlated with cardiovascular disease. It is still unclear whether hyperhomocyst(e)inemia observed in renal transplant recipients solely depends on the moderate reduction of renal function in these patients or if additional mechanisms are operative in this patient category. A recent study suggested that cyclosporine (CsA) increased plasma homocyst(e)ine concentration in interfering with folate-assisted remethylation of homocysteine. To confirm this hypothesis, we studied plasma homocyst(e)ine folic acid and cobalamin concentrations in 122 renal transplant recipients (104 on CsA and 18 not receiving CsA). After adjusting for age, gender, transplant duration and serum creatinine concentration, patients with and without CsA had similar plasma homocyst(e)ine concentrations (17.9 +/- 6.1 mumol/l in CsA(+)patients vs 17.1 +/- 5.6 mumol/l in CsA(-)patients; p = 0.3). Moreover, we found a significant inverse relationship between plasma homocyst(e)ine and folic acid concentrations in both CsA(+) (r = 0.218; p < 0.01) and CsA(-) (r = -0.678; p < 0.05) patients. Patients with a past history of cardiovascular incidents had higher plasma homocyst(e)ine concentrations than those without cardiovascular antecedent (20.5 +/- 7.8 mumol/l vs. 18.01 +/- 9.9 mumol/l; p < 0.05. To conclude: 1, We did not find any influence of CsA on plasma homocyst(e)ine concentrations. 2. We demonstrated that as in other patient category, plasma folic acid and homocyst(e)ine concentrations are significantly correlated in CsA(+) patients. 3. Homocyst(e)ine-lowering therapy would be prescribed in CsA(+) patients to allow correction of hyperhomocyst(e)inemia.

Topics: Arteriosclerosis; Case-Control Studies; Creatinine; Cyclosporine; Female; Folic Acid; Homocysteine; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Risk Factors; Vitamin B 12

Elevated plasma total homocysteine (tHcy), low B-vitamin intake, and genetic polymorphisms related to tHcy metabolism may play roles in coronary heart disease (CHD). More prospective studies are needed.. We used a prospective case-cohort design to determine whether tHcy-related factors are associated with incidence of CHD over an average of 3.3 years of follow-up in a biracial sample of middle-aged men and women. Age-, race-, and field center-adjusted CHD incidence was associated positively (P<0.05) with tHcy in women but not men, and CHD was associated negatively (P<0.05) with plasma folate (women only), plasma pyridoxal 5'-phosphate (both sexes), and vitamin supplementation (women only). However, after accounting for other risk factors, only plasma pyridoxal 5'-phosphate was associated with CHD incidence; the relative risk for the highest versus lowest quintile of pyridoxal 5'-phosphate was 0.28 (95% CI=0.1 to 0.7). There was no association of CHD with the C677T mutation of the methylenetetrahydrofolate reductase gene or with 3 mutations of the cystathionine beta-synthase gene.. Our prospective findings add uncertainty to conclusions derived mostly from cross-sectional studies that tHcy is a major, independent, causative risk factor for CHD. Our findings point more strongly to the possibility that vitamin B6 offers independent protection. Randomized trials, some of which are under way, are needed to better clarify the interrelationships of tHcy, B vitamins, and cardiovascular disease.

Topics: Arteriosclerosis; Cohort Studies; Coronary Disease; Dietary Supplements; Fasting; Female; Folic Acid; Homocysteine; Humans; Incidence; Male; Middle Aged; Polymorphism, Genetic; Prospective Studies; Pyridoxal Phosphate; Risk Factors; Vitamin B 12

An increased total plasma homocysteine level is an established risk factor for atherosclerotic vascular disease. The plasma level of homocysteine is influenced by both environmental and genetic factors. An important genetic determinant of plasma homocysteine is a common amino acid dimorphism (Ala222Val) in the methylenetetrahydrofolate reductase (MTHFR) gene. Individuals homozygous for the Val allele have significantly higher homocysteine levels than those with an Ala/Val or Ala/Ala genotype. Moreover, the Val/Val genotype has been claimed to be a strong genetic risk factor for atherosclerosis. The aim of the present study is: (1) to determine the risk associated with the MTHFR dimorphism by comparing the genotype distribution in patients with premature atherosclerosis with that in a group of healthy controls; and (2) to investigate the relationship between the MTHFR genotype and parameters of homocysteine metabolism. The patient group consisted of 257 consecutive referred individuals with angiographically proven premature ( <50 years of age) arterial disease (coronary, and/or peripheral vascular disease). A total of 272 healthy hospital workers without a history of vascular disease were selected as a control group. The MTHFR-genotype was determined by PCR and gel-electrophoresis. A methionine-loading test was performed on 245 patients, and, in addition to homocysteine, levels of folate and vitamin B12 were measured. We found a strong correlation between MTHFR genotype and plasma homocysteine levels both before and after methionine loading. In addition, the MTHFR genotype seems important for the inverse relationship between homocysteine and folate and vitamin B12 levels. Lastly, the MTHFR genotype distribution was not different between patient and control groups. MTHFR genotype is a strong determinant of plasma homocysteine levels. Moreover, the plasma level of folate, which by itself influences homocysteine levels, is also dependent on the MTHFR genotype. In Val/Val genotypes, low levels of both folate and B12 lead to a relatively large increase in homocysteine levels. Nevertheless, the MTHFR genotype does not increase the risk for premature coronary artery disease.

Topics: Adult; Age of Onset; Arteriosclerosis; DNA Mutational Analysis; Female; Folic Acid; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Oxidoreductases Acting on CH-NH Group Donors; Point Mutation; Risk Factors; Vitamin B 12

Fasting total plasma homocysteine levels were measured by rapid ion-exchange chromatography in 100 patients with symptomatic atherosclerotic peripheral vascular disease (PVD) and 100 age and sex-matched control subjects. Demographic data, biochemistry, hematology, and lipid fractions were measured in both groups, and clinical and vascular laboratory disease parameters were recorded for the patient group. Patients with hyperhomocysteinemia (defined as those with fasting homocysteine values exceeding the 90th percentile of the control range) were compared to patients with normal homocysteine with respect to the above parameters. Total fasting homocysteine concentrations were significantly higher in the patient group (28.8 +/- 14.9 mumol/l) than in the control subjects (20.3 +/- 11.3 mumol/l; p < 0.001). Homocysteine levels were also higher in males than in females in both the control and the patient groups. Homocysteine correlates positively only with age in the healthy controls (r = 0.291; p < 0.005) but not with other standard risk factors. Multivariate analysis of the biochemical risk factors confirmed that total plasma homocysteine concentration is an independent risk factor for PVD (p < 0.001). Hyperhomocysteinemia is not associated with vitamin B12 or folate deficiency states. Vitamin B12 concentration was 591 +/- 313 ng/l in the control group, and 682 +/- 405 ng/l in the patient group (p = NS). Serum folate concentration was lower in the controls (7.2 +/- 2.3 micrograms/l) than in the patients (8.3 +/- 2.0 micrograms/l, p < 0.001). Mild hyperhomocysteinemia was detected in 27% of the patients. Patients with hyperhomocysteinemia has a four-fold increase in risk of PVD relative to patients with a normal homocysteine level. There is no significant difference between the two groups with respect to patient demographics, biochemical risk factors, and disease pattern and severity.

Topics: Adult; Aged; Aged, 80 and over; Arteriosclerosis; Case-Control Studies; Chromatography, Ion Exchange; Fasting; Female; Homocysteine; Humans; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Risk Factors; Vitamin B 12

Plasma homocyst(e)ine [H(e)] levels correlate with the prevalence of arterial occlusive diseases. Recently, transesophageal echocardiography (TEE) has been used to evaluate patients with atherosclerotic plaques in the thoracic aorta. The purpose of this study was to determine whether H(e) levels correlate with the degree of atherosclerotic plaque in the thoracic aorta (ATH) as seen on TEE. Maximum plaque areas for three locations in the thoracic aorta (arch, proximal descending, and distal descending) were measured with TEE in 156 patients. Maximum plaque areas for these locations were added to yield an estimate of ATH. ATH and H(e) levels, and levels of folic acid, vitamin B12, and pyridoxal 5'-phosphate were measured in a double-blind manner. Univariate analysis demonstrated a significant correlation of H(e) with ATH (r = 0.3, p< 0.001). On multivariate analysis, H(e) was independently predictive of ATH (r for the model including H(e) was 0.63, p < 0.0001). Plasma H(e) levels are therefore significantly and independently correlated with the degree of atherosclerosis in the thoracic aorta.

Topics: Aged; Aorta, Thoracic; Aortic Diseases; Arteriosclerosis; Echocardiography, Transesophageal; Female; Folic Acid; Homocysteine; Humans; Male; Multivariate Analysis; Observer Variation; Pyridoxal Phosphate; Pyridoxine; Risk Factors; Vitamin B 12

Bioscientists, physicians and nutritionists are newly interested in the homocysteine-folate-cobalamin triad, in part because homocysteine may be important both in atherogenesis and thrombogenesis. Homocysteine imbalance may be an early marker for cobalamin disorders because cobalamin is a cofactor in remethylation of homocysteine to methionine.. In 139 men and 32 women of similar mean age of 65 years, we measured markers which have been cited as risk for atherosclerosis: serum homocysteine, folate, total cobalamin, holotranscobalamin I and II, (TCI and TCII), total serum cholesterol (SCHOL), high density lipoprotein cholesterol (HDLC), triglycerides (STG) as well as red blood cell (RBC) folate, food records and body composition by whole body counting of potassium-forty (40K).. Statistical relationships among the data showed healthy women had lower mean serum homocysteine and their mean RBC folate and TCI and TCII were higher than men. Eighty-three subjects had TCII much lower than 60 pg/ml (subnormal), yet only 11 of these men and two women had total cobalamin < 200 pg/ml (abnormal). Fifty-two subjects with serum homocysteine greater than 17.5 nmol/ml had TCII less than 60 pg/ml, suggesting serum homocysteine may be a marker for early cobalamin negative balance. None of the subjects in the study had serum folate below abnormal values, i.e., less than 1.6 mg/ml. All subjects had RBC folate within normal range. Serum homocysteine showed inverse relationship with RBC folate and serum total cobalamin, TCI and TCII.. 1) importance of using serum holotranscobalamin TCI and TCII as markers of cobalamin deficiency, 2) necessity to use documented quantitative components of dietary intake if strong comparisons are to be made among quantitative values of serum or plasma homocysteine, folate, cobalamin, and nutrients in food intake.

Topics: Adult; Aged; Aged, 80 and over; Animals; Arteriosclerosis; Biomarkers; Diet; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Transcobalamins; Vitamin B 12

Many epidemiologic studies have identified elevated plasma homocyst(e)ine as a risk factor for atherosclerosis and thromboembolic disease. To examined the relationship between vitamin intakes and plasma homocyst(e)ine, we analyzed dietary intake data from a case-control study of 322 middle-aged individuals with atherosclerosis in the carotid artery and 318 control subjects without evidence of this disease.. All of these individuals were selected from a probability sample of 15,800 men and women who participated in the Atherosclerosis Risk in Communities (ARIC) Study.. Plasma homocyst(e)ine was inversely associated with intakes of folate, vitamin B6, and vitamin B12 (controls only for this vitamin)--the three key vitamins in homocyst(e)ine metabolism. Among nonusers of vitamin supplement products, on average each tertile increase in intake of these vitamins was associated with 0.4 to 0.7 mumol/L decrease in plasma homocyst(e)ine. An inverse association of plasma homocyst(e)ine was also found with thiamin, riboflavin, calcium, phosphorus, and iron. Methionine and protein intake did not show any significant association with plasma homocyst(e)ine.. In almost all analyses, cases and controls showed similar associations between dietary variables and plasma homocyst(e)ine. Plasma homocyst(e)ine among users of vitamin supplement products was 1.5 mumol/L lower than that among nonusers. Further studies to examine possible causal relationships among vitamin intake, plasma homocyst(e)ine, and cardiovascular disease are needed.

Topics: Analysis of Variance; Arteriosclerosis; Carotid Arteries; Case-Control Studies; Diet; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Nutrition Surveys; Pyridoxine; Regression Analysis; Sampling Studies; United States; Vitamin B 12

An increased plasma homocysteine level is an independent risk factor for vascular disease. However, the pathological mechanisms by which homocysteine promotes atherosclerosis are not yet clearly defined. Arterial smooth muscle cells cultured in the presence of homocysteine grew to a higher density and produced and accumulated collagen at levels significantly above control values. Homocysteine concentrations as low as 50 mumol/L significantly increased both cell density and collagen production. Cell density increased by as much as 43% in homocysteine-treated cultures. Homocysteine increased collagen production in a dose-dependent manner. Smooth muscle cells treated with homocysteine at concentrations observed in patients with hyperhomocysteinemia had collagen synthesis rates as high as 214% of control values. Likewise, collagen accumulation in the cell layer was nearly doubled in homocysteine-treated cultures. Addition of aquacobalamin to homocysteine-treated cultures controlled the increase in smooth muscle cell proliferation and collagen production. These results indicate a cellular mechanism for the atherogenicity of homocysteine and provide insight into a potential preventive treatment.

Topics: Animals; Arteriosclerosis; Cell Division; Cells, Cultured; Collagen; Homocysteine; Male; Muscle, Smooth, Vascular; Rabbits; Risk Factors; Vitamin B 12

There is an excess prevalence of hyperhomocysteinemia in dialysis-dependent end-stage renal disease (ESRD) patients. Cross-sectional studies of the relationship between elevated total homocysteine (tHcy) levels and prevalent cardiovascular disease (CVD) in this patient population suffer from severe methodologic limitations. No prospective investigations examining the association between tHcy levels and the subsequent development of arteriosclerotic CVD outcomes among maintenance dialysis patients have been reported. To assess whether elevated plasma tHcy is an independent risk factor for incident CVD in dialysis-dependent ESRD patients, we studied 73 maintenance peritoneal dialysis or hemodialysis patients who received a baseline examination between March and December 1994, with follow-up through April 1, 1996. We determined the incidence of nonfatal and fatal CVD events, which included all validated coronary heart disease, cerebrovascular disease, and abdominal aortic/lower-extremity arterial disease outcomes. After a median follow-up of 17.0 months, 16 individuals experienced at least one arteriosclerotic CVD event. Cox proportional-hazards regression analyses, unadjusted and individually adjusted for creatinine, albumin, and total cholesterol levels, total/HDL cholesterol ratio, dialysis adequacy/residual renal function, baseline CVD, and the established CVD risk factors (ie, age, sex, smoking, hypertension, diabetes/glucose intolerance, and dyslipidemia) revealed that tHcy levels in the upper quartile (> or = 27.0 mumol/L) versus the lower three quartiles (< 27.0 mumol/L) were associated with relative risk estimates (hazards ratios, with 95% confidence intervals for the occurrence of (pooled) nonfatal and fatal CVD ranging from 3.0 to 4.4; 95% confidence intervals (1.1-8.1) to (1.6-12.2). We conclude that the markedly elevated fasting tHcy levels found in dialysis-dependent ESRD patients may contribute independently to their excess incidence of fatal and nonfatal CVD outcomes.

Topics: Adult; Aged; Arteriosclerosis; Blood Glucose; Cardiovascular Diseases; Cholesterol, HDL; Cohort Studies; Comorbidity; Diabetes Mellitus; Fasting; Female; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Proportional Hazards Models; Prospective Studies; Pyridoxine; Renal Dialysis; Single-Blind Method; Smoking; Treatment Outcome; Vitamin B 12

Moderate elevation of plasma homocyst(e)ine is associated with increased risk for atherosclerotic vascular disease. In a previous study, we observed impaired vascular function in nonatherosclerotic monkeys with moderate hyperhomocyst(e)inemia. In this study, we tested the hypothesis that dietary intervention to lower plasma homocyst(e)ine corrects vascular dysfunction in atherosclerotic monkeys. Cynomolgus monkeys were fed an atherogenic diet that produces both hypercholesterolemia and moderate hyperhomocyst(e)inemia. After 17 months, the atherogenic diet was supplemented with B vitamins (5 mg folic acid, 400 micrograms vitamin B-12, and 20 mg vitamin B-6 daily) for 6 months. Total plasma homocyst(e)ine decreased from 12.8 +/- 2.8 to 3.5 +/- 0.3 mumol/L (n = 9; mean +/- SE; P < .01) after vitamins were added to the diet, but plasma cholesterol remained elevated (522 +/- 63 versus 514 +/- 41 mg/dL; P > .05). In response to intra-arterial infusion of collagen, blood flow to the leg decreased by 30 +/- 3% and 38 +/- 5%, respectively, before and after vitamin supplementation (P > .05). In vivo responses of resistance vessels to endothelium-dependent vasodilators (acetylcholine or ADP) were impaired at baseline and did not improve after vitamin supplementation. In carotid artery studied ex vivo, relaxation to low doses of acetylcholine improved after vitamin supplementation, but maximal relaxation remained impaired. Ex vivo thrombomodulin anticoagulant activity was threefold higher in monkeys fed the atherogenic diet (with or without B vitamins) than in normal monkeys (P < .05). We conclude that normalization of plasma homocyst(e)ine is insufficient to restore normal vascular function in atherosclerotic monkeys with persistent hypercholesterolemia and that atherosclerosis, with or without hyperhomocyst(e)inemia, is associated with elevated thrombomodulin activity.

Topics: Acetylcholine; Adenosine Diphosphate; Animals; Arteriosclerosis; Carotid Arteries; Carotid Stenosis; Cholesterol; Collagen; Diet, Atherogenic; Enzyme Activation; Folic Acid; Homocysteine; Homocystine; Hypercholesterolemia; Leg; Macaca fascicularis; Nitroprusside; Protein C; Pyridoxine; Thrombomodulin; Vasodilation; Vasomotor System; Vitamin B 12

Elevated plasma homocysteine levels are recognized as an independent risk factor for atherosclerotic disease. It is not known (1) whether the severity of atherosclerotic disease is related to hyperhomocyst(e)inemia or (2) whether any such relation differs between fasting and post-methionine loading plasma homocysteine levels. Therefore, in 171 consecutive patients under 55 years of age with first symptoms of lower-limb disease, we examined the relation between severity of atherosclerosis and plasma homocysteine concentration. Severity of atherosclerotic disease was estimated from the prevalence of coronary artery disease and cerebrovascular disease and from the angiographic extent of lower-limb disease. Plasma homocysteine was measured after a period of fasting and in response to methionine loading (0.1 g/kg). In multivariate analysis, the prevalence of coronary artery disease plus cerebrovascular disease was related to both fasting and postmethionine homocysteine levels (odds ratio [OR] for the upper quartile versus the lower three quartiles, 2.8, 95% confidence interval [CI], 1.1 to 7.5; and OR 3.0, 95% CI, 1.1 to 7.8, respectively). The extent of lower-limb disease was weakly related to the fasting homocysteine level (partial correlation coefficient, .12; P = .17) and more strongly related to the postmethionine homocysteine level (partial correlation coefficient, .25; P = .003). These relations tended to be more pronounced in women than in men. They were independent of age, total serum cholesterol, blood pressure, and smoking habit. We concluded that the severity of atherosclerotic disease in young patients with lower-limb atherosclerotic disease is associated with high postmethionine and fasting homocysteine concentrations.

Topics: Adult; Arteriosclerosis; Cerebrovascular Disorders; Coronary Disease; Fasting; Female; Folic Acid; Homocysteine; Humans; Leg; Male; Methionine; Middle Aged; Pyridoxine; Risk Factors; Vitamin B 12

Topics: Angina Pectoris; Arteriosclerosis; Folic Acid; Homocysteine; Humans; Myocardial Infarction; Prospective Studies; Pyridoxine; Risk Factors; Vitamin B 12

A high level of total plasma homocysteine is a risk factor for atherosclerosis, which is an important cause of death in renal failure. We evaluated the role of this as a risk factor for vascular complications of end-stage renal disease.. Total fasting plasma homocysteine and other risk factors were documented in 176 dialysis patients (97 men, 79 women; mean age, 56.3 +/- 14.8 years). Folate, vitamin B12, and pyridoxal phosphate concentrations were also determined. The prevalence of high total homocysteine values was determined by comparison with a normal reference population, and the risk of associated vascular complications was estimated by multiple logistic regression. Total homocysteine concentration was higher in patients than in the normal population (26.6 +/- 1.5 versus 10.1 +/- 1.7 mumol/L; P < .01). Abnormally high concentrations (> 95th percentile for control subjects, 16.3 mumol/L) were seen in 149 patients (85%) with end-stage renal disease (P < .001). Patients with a homocysteine concentration in the upper two quintiles (> 27.8 mumol/L) had an independent odds ratio of 2.9 (CI, 1.4 to 5.8; P = .007) of vascular complications. B vitamin levels were lower in patients with vascular complications than in those without. Vitamin B6 deficiency was more frequent in patients than in the normal reference population (18% versus 2%; P < .01).. A high total plasma homocysteine concentration is an independent risk factor for atherosclerotic complications of end-stage renal disease. Such patients may benefit from higher doses of B vitamins than those currently recommended.

Topics: Aged; Aging; Arteriosclerosis; Female; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Male; Middle Aged; Odds Ratio; Osmolar Concentration; Peritoneal Dialysis, Continuous Ambulatory; Pyridoxine; Renal Dialysis; Risk Factors; Sex Distribution; Vitamin B 12

We describe a large family with hyperhomocysteinemia, the first to be reported in Poland. The proband's coronary complaints appeared at the age of 20, and by the age of 50 he had suffered extensive myocardial infarction. Examination of 17 persons from 4 generations revealed hyperhomocysteinemia in 2 daughters of the proband, while more discrete abnormalities were detected during methionine loading test in two other persons. Levels of cystathionone beta-syntetase and methyleno-FH4 reductase were normal in skin fibroblast culture. Treatment with folic acid and vitamin B12 led to 5-fold depression of plasma homocysteine in the proband, and complete normalization in the other treated member of the family.

Topics: Adult; Aged; Arteriosclerosis; Child; Child, Preschool; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Myocardial Infarction; Vitamin B 12

Long-term treatment of breast-cancer patients with the anti-oestrogen tamoxifen has been found to be associated with reduced cardiovascular mortality. Plasma homocysteine is an independent risk factor for atherosclerotic disease, and its level is determined by folate and cobalamin status, and possibly also by oestrogen status. We measured the effect of tamoxifen on plasma homocysteine, serum cholesterol, serum cobalamin and serum and erythrocyte folate in 31 post-menopausal women with breast cancer. The plasma homocysteine level was decreased by a mean value of 29.8% after 9-12 months and by 24.5% after 13-18 months of treatment. Tamoxifen suppressed serum cholesterol by mean values varying between 7.2% and 17.6% after 3 to 19 months of treatment. There was no correlation between changes in plasma homocysteine and serum cholesterol. These findings suggest that the homocysteine-lowering effect of tamoxifen may contribute to the reduction of cardiovascular mortality observed in patients on adjuvant therapy with tamoxifen.

Topics: Aged; Arteriosclerosis; Breast Neoplasms; Cholesterol; Cysteine; Female; Folic Acid; Homocysteine; Humans; Menopause; Middle Aged; Tamoxifen; Time Factors; Vitamin B 12

Moderate hyperhomocysteinemia may be a risk factor for atherosclerotic peripheral vascular disease (PVD). In order to develop PVD at an early age risk factors are more strongly expressed and hyperhomocysteinemia may be one such factor. Homocysteine is derived from methionine and is metabolised by cystathionine-synthase to cystathionine or remethylated to methionine. Cystathionine-synthase activity is dependent on vitamin B6 while the remethylation of homocysteine is dependent on vitamin B12 and folate. The present study analyses homocysteine in patients operated on for lower extremity ischaemia before the age of 50. Homocysteine before and after loading with methionine, vitamin B6, B12 and folate were measured at follow-up. The patients were compared to age- and sex-matched controls. Significantly more patients than controls had hyperhomocysteinemia, 16/58 vs. 4/65, defined as fasting total homocysteine above 18.6 mumol/l. Loading with methionine did not further discriminate between patients and controls. Smoking patients had higher levels of homocysteine than non-smoking patients or smoking and non-smoking controls. Smoking patients also had lower levels of vitamin B6. When comparing patients with suprainguinal, infrainguinal and multilevel disease the highest homocysteine levels were seen in the latter group. Also, in this group smoking patients had higher homocysteine levels. Multivariate analysis revealed that homocysteine was associated with low levels of vitamin B12, folate and smoking. Smoking therefore seems to be connected to increased homocysteine levels in patients with early development of atherosclerosis, partly explained by decreased levels of B6, B12 and folate.

Topics: Adult; Arteriosclerosis; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Ischemia; Male; Methionine; Middle Aged; Postoperative Complications; Pyridoxine; Risk Factors; Smoking; Vitamin B 12

In order to study the relation of homocysteine and lipid metabolism to atherogenesis, rabbits were fed a synthetic atherogenic diet and treated with parenteral thioretinaco (N-homocysteine thiolactonyl retinamido cobalamin), thioretinamide (N-homocysteine thiolactonyl retinamide) or homocysteine thiolactone hydrochloride. All three substances were found to increase dietary atherogenesis. Thioretinaco and thioretinamide increase total homocysteine of serum, but there is no effect of parenteral homocysteine thiolactone hydrochloride on serum homocysteine. The synthetic diet with corn oil significantly lowers serum homocysteine, compared either to baseline chow diet or to the synthetic diet with butter. Atherogenesis is correlated with total homocysteine, total cholesterol and LDL + VLDL cholesterol, and serum homocysteine is correlated with total cholesterol, LDL + VLDL, and HDL cholesterol in the total sample. Both synthetic diets elevate serum cholesterol, triglycerides and LDL + VLDL, but not HDL, compared to baseline values. Thioretinamide causes significant elevation of cholesterol and LDL + VLDL, compared to controls. The results show that increased dietary saturated fat and cholesterol cause deposition of lipids within the arteriosclerotic plaques produced by homocysteine, converting fibrous to fibrolipid plaques. Facilitation of atherogenesis is attributed to the effect of homocysteine on artery wall, either from parenteral homocysteine or from the increased synthesis of homocysteine from methionine, produced by thioretinaco and thioretinamide.

Topics: Animals; Arteriosclerosis; Diet, Atherogenic; Homocysteine; Lipids; Muscle, Smooth, Vascular; Rabbits; Tretinoin; Vitamin B 12

Cardiovascular lesions were observed at necropsy in five of six sheep which were subjected to an experimentally induced cobalt-vitamin B12 deficiency during a period of 34 weeks. The classical symptoms of cobalt-vitamin B12 deficiency (anorexia, cachexia, anaemia) were seen in all six sheep at week 20 of the experiment. Histologically, lesions of the auricular epicardium and myocardium consisted of a high concentration of inflammatory cells dominated by polynuclear eosinophils as well as the haemorrhagic inflammation of blood vessels accompanied by necrosis of auricular tissue. The similarity between the lesions observed in the present experiment and those seen in arteriosclerosis, led to the suggestion that a deficiency of vitamin B12 may be implicated in the pathogenesis of arteriosclerosis. A hypothesis is advanced in this respect.

Topics: Animals; Arteriosclerosis; Cardiovascular Diseases; Cobalt; Myocardium; Necrosis; Sheep; Sheep Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Anti-Bacterial Agents; Arteriosclerosis; Basilar Artery; Cerebrovascular Disorders; Chronic Disease; Deoxyribonucleases; Diabetic Neuropathies; Diuretics; Facial Nerve; Facial Paralysis; Female; Herpes Zoster; Humans; Hypertension; Ischemia; Male; Middle Aged; Physical Therapy Modalities; Prednisolone; Recurrence; Tonsillitis; Vertebral Artery; Vitamin B 12

Topics: Arteriosclerosis; Coronary Disease; Exercise Therapy; Female; Humans; Hypolipidemic Agents; Iodine; Male; Middle Aged; Parasympatholytics; Vitamin B 12

Topics: Aminobenzoates; Animals; Arteries; Arteriosclerosis; Ascorbic Acid; Biotin; Carotenoids; Chickens; Choline; Dogs; Folic Acid; Humans; Inositol; Nicotinic Acids; Pyridoxine; Rabbits; Riboflavin; Thiamine; Vitamin A; Vitamin B 12; Vitamin E; Vitamins

Topics: Aged; Arteriosclerosis; Cholesterol; Choline; Drug Combinations; Fatty Acids; Female; Flavin Mononucleotide; Heparin; Humans; Hypercholesterolemia; Hyperlipidemias; Male; Middle Aged; Niacinamide; Phospholipids; Triglycerides; Vitamin B 12

Topics: Adult; Aged; Arteriosclerosis; Biliary Tract Diseases; Carbohydrate Metabolism; Coronary Disease; Diabetes Mellitus; Diabetic Nephropathies; Female; Humans; Hypertension; Male; Middle Aged; Nucleotides; Obesity; Pyridoxine; Taurine; Vitamin B 12

Topics: Adenine; Aging; Arteriosclerosis; Catecholamines; DNA; Humans; Lipoproteins; Methionine; Methylation; Methyltransferases; Phosphatidylcholines; Phospholipids; RNA; S-Adenosylmethionine; Vitamin B 12

Topics: Adult; Aged; Arteriosclerosis; Cerebrovascular Disorders; Dementia; Female; Hemiplegia; Humans; Hypertension; Male; Middle Aged; Nucleotides; Pyridoxine; Taurine; Vitamin B 12

Topics: Amino Acid Metabolism, Inborn Errors; Amino Acids; Aminobutyrates; Arteries; Arteriosclerosis; Child; Diet; Homocysteine; Homocystinuria; Humans; Infant, Newborn; Isomerases; Kidney; Ligases; Male; Malonates; Methionine; Vitamin B 12

Topics: Adolescent; Adult; Age Factors; Aged; Aorta; Aorta, Thoracic; Aortic Diseases; Arteries; Arteriosclerosis; Biological Assay; Blood Vessels; Child; Child, Preschool; Coronary Vessels; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Pulmonary Artery; Vena Cava, Inferior; Vitamin B 12

Topics: Adult; Aged; Arteriosclerosis; Ascorbic Acid; Calcium; Cholesterol; Coronary Disease; Electrocardiography; Female; Gluconates; Humans; Hypothyroidism; Male; Middle Aged; Niacinamide; Pantothenic Acid; Riboflavin; Thiamine; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Thyroxine; Vitamin B 12

Topics: Anemia, Pernicious; Arteriosclerosis; Cobalt Isotopes; Computers; Humans; Multiple Sclerosis; Polycythemia Vera; Radiometry; Statistics as Topic; Time Factors; Vitamin B 12

Topics: Aged; Arteriosclerosis; Cholesterol; Female; Humans; Male; Middle Aged; Phosphatidylcholines; Prothrombin; Thiamine; Vitamin B 12; Vitamin E

Topics: Aged; Arteriosclerosis; Cholesterol; Female; Humans; Liver Diseases; Liver Extracts; Liver Function Tests; Male; Nucleosides; Uridine; Vitamin B 12

Topics: Adenine Nucleotides; Aged; Arteriosclerosis; Female; Hepatitis; Humans; Hypertension; Joint Diseases; Male; Spinal Diseases; Thiamine Pyrophosphate; Vitamin B 12

Topics: Adult; Aged; Arteriosclerosis; Female; Humans; Hypertension; Male; Middle Aged; Vitamin B 12

Topics: Adolescent; Adult; Aged; Arteriosclerosis; Blood; Cholecystitis; Cobalt Isotopes; Colitis, Ulcerative; Creatine; Female; Glomerular Filtration Rate; Glomerulonephritis; Goiter; Humans; Hypertension; Inulin; Male; Middle Aged; Nephrocalcinosis; Pyelonephritis; Scleroderma, Systemic; Urine; Vitamin B 12

Topics: Aged; Arteriosclerosis; Female; Humans; Hypertension; Male; Middle Aged; Niacinamide; Reserpine; Rutin; Vitamin B 12

Topics: Aging; Arteriosclerosis; Atherosclerosis; Cysteine; Folic Acid; Humans; Metabolism; Pantothenic Acid; Rabbits; Research; Vitamin B 12; Vitamin B Complex

Topics: Arteriosclerosis; Blood Glucose; Blood Proteins; Cataract; Cholesterol; Classification; Diabetes Mellitus; Diabetic Retinopathy; Eye Manifestations; Fibrinolysin; Humans; Japan; Pathology; Retinitis; Statistics as Topic; Vitamin B 12

Topics: Arteriosclerosis; Blood Chemical Analysis; Diabetes Mellitus; Diabetic Angiopathies; Geriatrics; Humans; Vitamin B 12; Vitamin B Complex

Topics: Arteriosclerosis; Biological Transport; Cobalt Isotopes; Corrinoids; Humans; Hypercholesterolemia; Ileum; Intestinal Absorption; Metabolism; Physiology; Surgical Procedures, Operative; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Arteriosclerosis; Atherosclerosis; Fibrinolysis; Hematinics; Humans; Vitamin B 12

Topics: Anemia; Anemia, Pernicious; Arteriosclerosis; Atherosclerosis; Avitaminosis; Folic Acid; Geriatrics; Humans; Vitamin B 12; Vitamin B Complex

Topics: Arteriosclerosis; Atherosclerosis; Cholesterol; Corrinoids; Hematinics; Humans; Lecithins; Phosphatidylcholines; Thiamine; Vitamin B 12

Topics: Arteriosclerosis; Atherosclerosis; Choline; Fatty Acids; Folic Acid; Hematinics; Humans; Lipid Metabolism; Lipotropic Agents; Niacin; Nicotinic Acids; Proteins; Pyridoxine; Vitamin B 12

Topics: Androsterone; Arteriosclerosis; Cholesterol; Diet; Diet Therapy; Estrogens; Flavonoids; Heparin; Lipids; Methionine; Sterols; Thyroxine; Vitamin B 12

Topics: Arteriosclerosis; Atherosclerosis; Corrinoids; Folic Acid; Hematinics; Humans; Vitamin B 12

The serum vitamin B(12) level was abnormally high in 14 out of 32 cases of renal failure. This was probably due to impaired excretion of the vitamin, but the results of measurements of the rate of excretion of radioactive vitamin B(12) did not provide unequivocal evidence on this point; other possible explanations are discussed. Renal failure must be added to the causes of high serum B(12) levels.

Topics: Arteriosclerosis; Glomerulonephritis; Humans; Hypertension; Hypertension, Malignant; Kidney; Kidney Diseases; Nephritis; Nephrocalcinosis; Polycystic Kidney Diseases; Pyelonephritis; Renal Insufficiency; Vitamin B 12

Topics: Arteriosclerosis; Atherosclerosis; Blood Proteins; Cholesterol; Humans; Lipids; Lipoproteins; Vitamin B 12

Topics: Arteriosclerosis; Hematinics; Heparin; Intercellular Signaling Peptides and Proteins; Lipoprotein Lipase; Peptides; Vitamin B 12

Topics: Arteriosclerosis; Atherosclerosis; Hematinics; Vitamin B 12

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Basal Metabolism; Corrinoids; Hematinics; Humans; Vitamin B 12; Vitamin B Complex; Vitamins

Topics: Arteriosclerosis; Atherosclerosis; Blood Coagulation; Cholesterol; Humans; Phospholipids; Prothrombin; Serum; Vitamin B 12

Topics: Animals; Arteriosclerosis; Atherosclerosis; Cholesterol; Corrinoids; Hematinics; Lagomorpha; Rabbits; Vitamin B 12

Topics: Arteriosclerosis; Corrinoids; Geriatrics; Hematinics; Vitamin B 12

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Cholesterol; Humans; Vitamin B 12; Vitamins

Topics: Arteriosclerosis; Betaine; Choline; Corrinoids; Glycine; Humans; Lipotropic Agents; Liver Extracts; Vitamin B 12; Vitamin B Complex