vitamin-b-12 and Coronary-Disease

Topics: Coronary Disease; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Nurse's Role; Patient Education as Topic; Primary Prevention; Risk Factors; Vitamin B 12; Vitamin B 6

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

In the prevention of coronary heart disease the aim to achieve the target cholesterol and triglyceride levels and the maximal risk reduction leads to the combination of lipid lowering agents. The importance of the combination is supported by the fact that in monotherapy use of the high dose of the drugs, the lipid lowering effect is modest and the side effects are more frequent. The combined therapy is expected to be used more frequently despite the fact, that the improperly applied combination could have serious unfavourable effects. The authors review the advantages and drawbacks of the fibrate-statin combination, which could be used in the most frequent lipid abnormality, the high cholesterol and high triglyceride level, when the combination of micronized fenofibrate and fluvastatin is recommended. Beside the co-administration of other lipid lowering drugs (nicotine acid and resins), it is discussed the combination of statins and fibrates with a new, cholesterol absorption inhibitor, ezetimibe, a well tolerated drug with advantageous safety profile. Considering further metabolic risks the combination of lipid lowering drugs with glitazones, hormone replacement therapy, homocysteine reducing agents is as well highlighted.

Topics: Anticholesteremic Agents; Apolipoproteins; Azetidines; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Drug Therapy, Combination; Ezetimibe; Fatty Acids, Monounsaturated; Fenofibrate; Fluvastatin; Folic Acid; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypolipidemic Agents; Indoles; Lipids; Pravastatin; Simvastatin; Triglycerides; Vitamin B 12; Vitamin B 6

Although vitamin deficiency is encountered infrequently in developed countries, inadequate intake of several vitamins is associated with chronic disease.. To review the clinically important vitamins with regard to their biological effects, food sources, deficiency syndromes, potential for toxicity, and relationship to chronic disease.. We searched MEDLINE for English-language articles about vitamins in relation to chronic diseases and their references published from 1966 through January 11, 2002.. We reviewed articles jointly for the most clinically important information, emphasizing randomized trials where available.. Our review of 9 vitamins showed that elderly people, vegans, alcohol-dependent individuals, and patients with malabsorption are at higher risk of inadequate intake or absorption of several vitamins. Excessive doses of vitamin A during early pregnancy and fat-soluble vitamins taken anytime may result in adverse outcomes. Inadequate folate status is associated with neural tube defect and some cancers. Folate and vitamins B(6) and B(12) are required for homocysteine metabolism and are associated with coronary heart disease risk. Vitamin E and lycopene may decrease the risk of prostate cancer. Vitamin D is associated with decreased occurrence of fractures when taken with calcium.. Some groups of patients are at higher risk for vitamin deficiency and suboptimal vitamin status. Many physicians may be unaware of common food sources of vitamins or unsure which vitamins they should recommend for their patients. Vitamin excess is possible with supplementation, particularly for fat-soluble vitamins. Inadequate intake of several vitamins has been linked to chronic diseases, including coronary heart disease, cancer, and osteoporosis

Topics: Ascorbic Acid; Avitaminosis; Blood Coagulation; Breast Neoplasms; Carotenoids; Chronic Disease; Colorectal Neoplasms; Coronary Disease; Dietary Supplements; Female; Folic Acid; Fractures, Bone; Humans; Lung Neoplasms; Male; Neoplasms; Neural Tube Defects; Prostatic Neoplasms; Risk Factors; Vitamin A; Vitamin B 12; Vitamin B 6; Vitamin D; Vitamin E; Vitamin K; Vitamins

Homocyst(e)ine, a sulphur-containing amino acid, is an intermediate formed during the metabolism of the essential amino acid methionine. Biological and epidemiological evidence suggest that elevated plasma levels of homocyst(e)ine are a risk factor for atherosclerosis and coronary heart disease (CHD). In the general US population, hyperhomocyst(e)inaemia is common and most often due to mild nutritional deficiencies in the B vitamins (folic acid, vitamin B(12) and vitamin B(6)). While high homocyst(e)ine levels can be effectively lowered using folic acid and other B vitamins, it is unknown whether such vitamin therapy will lead to clinical benefits. Given that strategies for homocyst(e)ine-lowering are safe and inexpensive, however, even small reductions in CHD risk will be highly cost effective. Thus, it may be prudent for patients to ensure an adequate daily intake of dietary folic acid and other B vitamins and for physicians to screen high-risk adults such as those with established CHD as we await definitive results from ongoing clinical trials.

Topics: Coronary Disease; Dietary Supplements; Economics, Pharmaceutical; Female; Folic Acid; Food, Fortified; Homocysteine; Humans; Male; Vitamin B 12; Vitamin B 6

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

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

During the last decade, lipid lowering agents, in particular statins, have become increasingly important in the treatment of cardiovascular diseases and dyslipidaemias. This might imply that emphasis on diet and supplementary nutrients do not receive sufficient attention.. On the basis of studies of the literature, the scientific documentation for a possible beneficial effect of the following elements are reviewed: intake of fat, fish and fish oil, alpha-linolenic acid, folic acid, vitamin B6 and vitamin B12, nuts, plant sterols and psyllium.. Reduced intake of saturated fat causes improvement in serum lipid values and prevents cardiovascular events. Intake of fish, fish oils and alpha-linolenic acid has positive effects on several clinical end points, often without marked decrease in serum cholesterol. Homocysteine appears to be an independent risk factor for cardiovascular diseases, but a causal relationship remains to be proven. The cofactors folic acid, vitamin B6 and B12 reduce the homocysteine level, but effects of this intervention on hard clinical end points are lacking. There are indications that intake of nuts can prevent coronary events. Plant sterols and psyllium in the diet reduce cholesterol levels.. Thus, dietary intervention is important in the prevention and treatment of coronary heart disease. Also when drug treatment is indicated, a focus on diet and nutrient supplementation is highly warranted. Some nutrients may have preventive effect in relation to coronary events, despite their small effect on cholesterol levels.

Topics: Coronary Disease; Dietary Fats; Dietary Supplements; Feeding Behavior; Female; Fish Oils; Folic Acid; Homocysteine; Humans; Lipoproteins; Male; Nutritional Physiological Phenomena; Nuts; Phytosterols; Pyridoxine; Randomized Controlled Trials as Topic; Risk Factors; Vitamin B 12

To summarize results of clinical trials investigating the role of homocysteine (tHcy) as a risk factor for coronary artery disease (CAD) and the role of vitamin therapy (folic acid and vitamins B6 and B12) in primary and secondary prevention of CAD.. MEDLINE was searched from January 1976 to January 1999 to locate cross-sectional, retrospective and prospective cohort studies and meta-analyses on CAD using the MeSH words homocysteine, folic acid, vitamins B6 and B12, and coronary artery or heart disease.. Elevated tHcy levels are prevalent; most retrospective and cross-sectional studies show an association with increased risk of CAD. Results from recent prospective studies are less consistent. Folic acid, alone or with vitamins B6 and B12, reduces tHcy concentrations in the blood. Results from ongoing randomized controlled trials could determine the effect of vitamins B6 and B12 and folic acid supplementation on CAD-related morbidity and mortality and could indicate whether routine supplementation with these vitamins should be advocated. Before mass screening for tHcy can be done, the tHcy assay must be standardized.. The role of homocysteine and vitamins B6 and B12 in managing CAD is unclear. Routine screening is not recommended.

Topics: Clinical Trials as Topic; Coronary Disease; Diet; Folic Acid; Homocysteine; Humans; Pyridoxine; Risk Factors; Vitamin B 12

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

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

Topics: Age Factors; Animals; Blood Coagulation; Cerebrovascular Disorders; Chemical and Drug Induced Liver Injury; Contraceptives, Oral; Contraceptives, Oral, Hormonal; Coronary Disease; Folic Acid; Humans; Hypertension; Metabolism; Myocardial Infarction; Neoplasms; Progestins; Skin; Smoking; Teratogens; Thromboembolism; Time Factors; Vitamin B 12

In observational studies, elevated plasma total homocysteine levels have been positively associated with ischemic stroke risk. However the utility of homocysteine-lowering therapy to reduce that risk has not been confirmed by randomized trials.. To determine whether high doses of folic acid, pyridoxine (vitamin B6), and cobalamin (vitamin B12), given to lower total homocysteine levels, reduce the risk of recurrent stroke over a 2-year period compared with low doses of these vitamins.. Double-blind randomized controlled trial (September 1996-May 2003).. 3680 adults with nondisabling cerebral infarction at 56 university-affiliated hospitals, community hospitals, private neurology practices, and Veterans Affairs medical centers across the United States, Canada, and Scotland.. All participants received best medical and surgical care plus a daily multivitamin containing the US Food and Drug Administration's reference daily intakes of other vitamins; patients were randomly assigned to receive once-daily doses of the high-dose formulation (n = 1827), containing 25 mg of pyridoxine, 0.4 mg of cobalamin, and 2.5 mg of folic acid; or the low-dose formulation (n = 1853), containing 200 microg of pyridoxine, 6 microg of cobalamin and 20 microg of folic acid.. Recurrent cerebral infarction (primary outcome); coronary heart disease (CHD) events and death (secondary outcomes).. Mean reduction of total homocysteine was 2 micromol/L greater in the high-dose group than in the low-dose group, but there was no treatment effect on any end point. The unadjusted risk ratio for any stroke, CHD event, or death was 1.0 (95% confidence interval [CI], 0.8-1.1), with chances of an event within 2 years of 18.0% in the high-dose group and 18.6% in the low-dose group. The risk of ischemic stroke within 2 years was 9.2% for the high-dose and 8.8% for the low-dose groups (risk ratio, 1.0; 95% CI, 0.8-1.3) (P =.80 by log-rank test of the primary hypothesis of difference in ischemic stroke between treatment groups). There was a persistent and graded association between baseline total homocysteine level and outcomes. A 3- micromol/L lower total homocysteine level was associated with a 10% lower risk of stroke (P =.05), a 26% lower risk of CHD events (P<.001), and a 16% lower risk of death (P =.001) in the low-dose group and a nonsignificantly lower risk in the high-dose group by 2% for stroke, 7% for CHD events, and 7% for death.. In this trial, moderate reduction of total homocysteine after nondisabling cerebral infarction had no effect on vascular outcomes during the 2 years of follow-up. However, the consistent findings of an association of total homocysteine with vascular risk suggests that further exploration of the hypothesis is warranted and longer trials in different populations with elevated total homocysteine may be necessary.

Topics: Adult; Aged; Coronary Disease; Double-Blind Method; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Myocardial Infarction; Recurrence; Risk; Stroke; Treatment Outcome; Vitamin B 12; Vitamin B 6

Vitamin therapy to lower homocysteine levels has recently been recommended for the prevention of restenosis after coronary angioplasty. We tested the effect of a combination of folic acid, vitamin B6, and vitamin B12 (referred to as folate therapy) on the risk of angiographic restenosis after coronary-stent placement in a double-blind, multicenter trial.. A total of 636 patients who had undergone successful coronary stenting were randomly assigned to receive 1 mg of folic acid, 5 mg of vitamin B6, and 1 mg of vitamin B12 intravenously, followed by daily oral doses of 1.2 mg of folic acid, 48 mg of vitamin B6, and 60 microg of vitamin B12 for six months, or to receive placebo. The angiographic end points (minimal luminal diameter, late loss, and restenosis rate) were assessed at six months by means of quantitative coronary angiography.. At follow-up, the mean (+/-SD) minimal luminal diameter was significantly smaller in the folate group than in the placebo group (1.59+/-0.62 mm vs. 1.74+/-0.64 mm, P=0.008), and the extent of late luminal loss was greater (0.90+/-0.55 mm vs. 0.76+/-0.58 mm, P=0.004). The restenosis rate was higher in the folate group than in the placebo group (34.5 percent vs. 26.5 percent, P=0.05), and a higher percentage of patients in the folate group required repeated target-vessel revascularization (15.8 percent vs. 10.6 percent, P=0.05). Folate therapy had adverse effects on the risk of restenosis in all subgroups except for women, patients with diabetes, and patients with markedly elevated homocysteine levels (15 micromol per liter or more) at baseline.. Contrary to previous findings, the administration of folate, vitamin B6, and vitamin B12 after coronary stenting may increase the risk of in-stent restenosis and the need for target-vessel revascularization.

Topics: Aged; Coronary Angiography; Coronary Disease; Coronary Restenosis; Coronary Vessels; Double-Blind Method; Drug Therapy, Combination; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Risk Factors; Stents; Treatment Failure; Vitamin B 12; Vitamin B 6

We evaluated the effect of therapy with folic acid and cobalamin on coronary endothelial function, expressed as a change in volumetric coronary blood flow (CBF), in hyperhomocysteinemic patients with coronary artery disease (CAD).. Hyperhomocysteinemia is an independent risk factor for CAD. The mechanism responsible for this increased risk is unclear, but it is generally assumed that hyperhomocysteinemia causes endothelial dysfunction. It is unknown whether lowering plasma homocysteine levels with folic acid and cobalamin improves coronary endothelial function in patients with hyperhomocysteinemia and symptomatic CAD.. Fifteen patients scheduled for elective percutaneous transluminal coronary angioplasty (PTCA) with plasma homocysteine levels of >or=16 micromol/l were randomized for six months of treatment with folic acid 5 mg and cobalamin 400 microg daily or placebo. Coronary endothelial function was evaluated in a non-PTCA vessel using acetylcholine infusion in dosages of 10(-8) M, 10(-7) M, and 10(-6) M. Endothelium- dependent CBF is determined using intracoronary Doppler velocity and quantitative coronary angiography at baseline and after six months.. In the folic acid/cobalamin treated group, CBF increased after acetylcholine infusion with 96% (standard deviation 54; 95% confidence interval [CI]: 44% to 154%) compared with a decrease of 16% (standard deviation 35; 95% CI: -20% to +30%) of the CBF in the placebo-treated group (p < 0.005).. This is the first prospective randomized placebo-controlled intervention study evaluating coronary endothelial function in hyperhomocysteinemic patients with CAD. Our results suggest that coronary endothelial function improves after treatment with folic acid and cobalamin.

Topics: Adult; Aged; Coronary Circulation; Coronary Disease; Coronary Vessels; Endothelium, Vascular; Female; Folic Acid; Humans; Hyperhomocysteinemia; Male; Middle Aged; Prospective Studies; Vitamin B 12

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

The purpose of this study was to determine whether lowering homocysteine levels with folic acid, with or without antioxidants, will improve endothelial dysfunction in patients with coronary artery disease (CAD).. Elevated plasma homocysteine levels are a risk factor for atherosclerosis. Homocysteine may promote atherogenesis through endothelial dysfunction and oxidative stress.. In a double-blind, placebo-controlled, randomized trial, we used vascular ultrasound to assess the effect of folic acid alone or with antioxidants on brachial artery endothelium-dependent flow-mediated dilation (FMD). Seventy-five patients with CAD (screening homocysteine level > or =9 micromol/liter) were randomized equally to one of three groups: placebo, folic acid alone or folic acid plus antioxidant vitamins C and E. Patients were treated for four months. Plasma folate, homocysteine, FMD and nitroglycerin-mediated dilation were measured before and after four months of treatment.. Plasma folate, homocysteine and FMD were unchanged in the placebo group. Compared with placebo, folic acid alone increased plasma folate by 475% (p < 0.001), reduced plasma homocysteine by 11% (p = 0.23) and significantly improved FMD from 3.2 +/- 3.6% to 5.2 +/- 3.9% (p = 0.04). The improvement in FMD correlated with the reduction in homocysteine (r = 0.5, p = 0.01). Folic acid plus antioxidants increased plasma folate by 438% (p < 0.001), reduced plasma homocysteine by 9% (p = 0.56) and insignificantly improved FMD from 2.6 +/- 2.4% to 4.0 +/- 3.7% (p = 0.45), as compared with placebo. Nitroglycerin-mediated dilation did not change significantly in any group.. Folic acid supplementation significantly improved endothelial dysfunction in patients with coronary atherosclerosis. Further clinical trials are required to determine whether folic acid supplementation may reduce cardiovascular events.

Topics: Aged; Antioxidants; Ascorbic Acid; Blood Circulation; Coronary Disease; Double-Blind Method; Endothelium, Vascular; Female; Folic Acid; Homocysteine; Humans; Lipids; Male; Malondialdehyde; Middle Aged; Nitroglycerin; Vasodilation; Vasodilator Agents; Vitamin B 12; Vitamin E

Hyperhomocysteinemia is an independent risk factor for coronary heart disease (CHD). Dietary supplementation with B vitamins lowers plasma homocysteine by up to 30%. However, little is known about the potential beneficial effects of homocysteine lowering on vascular function in patients with CHD.. We investigated 89 men with CHD (aged 56 [range 39 to 67] years). Brachial artery flow-mediated dilatation (endothelium dependent) and nitroglycerin-induced dilatation (endothelium independent) were measured before and 8 weeks after treatment with either (1) folic acid (5 mg) and vitamin B(12) (1 mg) daily (n=59) or (2) placebo (n=30). Total, protein-bound, and free plasma homocysteine, serum folate, and vitamin B(12) were measured at baseline and at 8 weeks. Flow-mediated dilatation improved after treatment with B vitamins (2.5+/-3.2% to 4.0+/-3.7%, P:=0.002) but not placebo (2.3+/-2.6% to 1.9+/-2.6%, P:=0.5). Vitamin therapy lowered plasma concentrations of total homocysteine (from 13.0+/-3.4 to 9.3+/-1.9 micromol/L, P:<0.001), protein-bound homocysteine (from 8.7+/-2.8 to 6.2+/-1.4 micromol/L, P:<0.001), and free homocysteine (from 4.3+/-1.2 to 3.0+/-0.6 micromol/L, P:<0.001) and raised concentrations of serum folate (from 10.3+/-4.3 to 31.2+/-10.8 ng/mL, P:<0.001) and vitamin B(12) (from 314+/-102 to 661+/-297 pg/mL, P:<0.001). In regression analysis, improved flow-mediated dilatation correlated closely with the reduction in free plasma homocysteine (r=-0.26, P:=0.001), independent of changes in protein-bound homocysteine, folate, and vitamin B(12). Nitroglycerin-induced dilatation was unchanged after both B vitamins and placebo.. Folic acid and vitamin B(12) supplementation improves vascular endothelial function in patients with CHD, and this effect is likely to be mediated through reduced concentrations of free plasma homocysteine concentrations. Our data support the view that lowering homocysteine, through B vitamin supplementation, may reduce cardiovascular risk.

Topics: Adult; Aged; Blood Glucose; Brachial Artery; Cholesterol; Cholesterol, HDL; Coronary Disease; Dietary Supplements; Double-Blind Method; Endothelium, Vascular; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Multivariate Analysis; Nitroglycerin; Regression Analysis; Triglycerides; Ultrasonography; Vasodilator Agents; Vitamin B 12

An increased plasma homocysteine concentration is a risk factor for atherosclerosis. Folic acid lowers homocysteine but the optimal dose in patients with coronary artery disease (CAD) is unclear. This placebo-controlled, single-blind, dose-ranging study evaluates the effect of low-dose folic acid on homocysteine levels in 95 patients aged 61 +/- 11 years (mean +/- SD) with documented CAD. Patients in each group were given either placebo or 1 of 3 daily supplements of folic acid (400 microg, 1 mg, or 5 mg) for 3 months. Each active treatment arm also received 500 microg vitamin B12 and 12.5 mg vitamin B6. Total plasma homocysteine levels were measured after 30 and 90 days. Folic acid 400 microg reduced homocysteine levels from 13.8 +/- 8.8 to 9.6 +/- 2.0 micromol/L at 90 days (p = 0.001). On 1- and 5-mg folic acid, levels decreased from 13.0 +/- 6.4 to 9.8 +/- 4.0 micromol/L (p = 0.001) and from 14.8 +/- 6.9 to 9.7 +/- 3.3 micromol/L (p < 0.001), respectively. The decrease was similar in all treatment groups. There was no significant change with placebo. Although the sample size is small, these findings suggest that daily administration of 400 microg/day folic acid combined with vitamin B12 and vitamin B6 may be equivalent to higher doses in reducing homocysteine levels in patients with CAD.

Topics: Coronary Disease; Female; Folic Acid; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Pyridoxine; Single-Blind Method; Vitamin B 12

It is known that the metabolism of homocysteine (Hcy) depends on the vitamins B6, B12 and folate, and furthermore that metformin reduces serum vitamin B12 levels. In order to investigate whether metformin treatment affects serum total Hcy (tHcy) levels we performed an open, prospective, randomised study in 60 non-diabetic male patients with cardiovascular disease. After a 4-week run-in period with lovastatin 40 mg day-1, and diet and lifestyle advice, patients were randomised into two groups, both continuing the run-in treatment. One group received metformin up to 2000 mg day-1, whereas the control group got no additional treatment. After 12 and 40 weeks of metformin treatment, tHcy levels increased moderately but significantly by 7.2% (p < 0.05) and 13.8% (p < 0.05) in the metformin group relative to the control group, whereas serum vitamin B12 levels decreased by 13.4% (p < 0.0005) and 17.7% (p < 0.0005), respectively. Serum folate levels did not change after 12 weeks, but decreased by 8.0% after 40 weeks (p = 0.061) relative to the control group. Serum levels of total cysteine and methylmalonic acid (MMA) did not change. In conclusion, metformin treatment increased tHcy levels and decreased levels of vitamin B12 and folate. Since MMA levels were unchanged, it remains an open question whether the increase in tHcy levels is secondary to reduced vitamin B12 levels, folate levels or a combination of both.

Topics: Adult; Coronary Disease; Cysteine; Folic Acid; Homocysteine; Humans; Hypoglycemic Agents; Male; Metformin; Methylmalonic Acid; Middle Aged; Vitamin B 12

Topics: Adult; Aged; Clinical Trials as Topic; Coronary Disease; Estradiol; Humans; Lipid Metabolism; Male; Middle Aged; Testosterone; Vitamin B 12

The mainstay of treating patients with phenylketonuria (PKU) is based on a Phe-restricted diet, restrictive in natural protein combined with Phe-free L-amino acid supplements and low protein foods. This PKU diet seems to reduce atherogenesis and confer protection against cardiovascular diseases but the results from the few published studies have been inconclusive. The aim of our study was to evaluate the relationship between the lipid profile and several treatment-related risk factors in patients with hyperphenylalaninaemia (HPA) in order to optimize their monitoring.. We conducted a cross-sectional multicentre study. A total of 141 patients with HPA were classified according to age, phenotype, type of treatment and dietary adherence. Annual median blood phenylalanine (Phe) levels, Phe tolerance, anthropometric measurements, blood pressure (BP) and biochemical parameters [(triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), apolipoprotein A (ApoA), apolipoprotein B (ApoB), vitamin B12, total homocysteine (tHcy), Methionine (Met), high sensitivity C-Reactive Protein (hsCRP)] were collected for each patient.. Plasma TC levels were lower in patients with PKU than in the mild-HPA group (150 ± 31 vs. 164 ± 22 mg/dL), and there was a weak inverse correlation between plasma TC and Phe levels. HDL-C, LDL-C, ApoA and ApoB levels were lower in the PKU group than in mild-HPA. Patients with PKU had higher systolic BP than the mild-HPA group and there was found a quadratic correlation between median Phe levels and systolic BP (p = 6.42e(-5)) and a linear correlation between median Phe levels and diastolic BP (p = 5.65e(-4)). In overweight or obese PKU patients (24.11 %), biochemical parameters such as TC, triglycerides, LDL-C, tHcy, hsCRP and BP were higher. By contrast, HDL-C was lower in these patients.. Our data show a direct correlation between lipid profile parameters and good adherence to the diet in PKU patients. However, lipid profile in overweight or obese patients displayed an atherogenic profile, in addition to higher hsCRP concentrations and BP. Our study contributes to a better understanding of the relationship between phenotype and treatment in patients with HPA, which could be useful in improving follow-up strategies and clinical outcome.. Research Ethics Committee of Santiago-Lugo 2015/393. Registered 22 September 2015, retrospectively registered.

Topics: Apolipoproteins A; Apolipoproteins B; Blood Pressure; C-Reactive Protein; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Cross-Sectional Studies; Female; Homocysteine; Humans; Lipids; Male; Methionine; Phenylketonurias; Risk Factors; Triglycerides; Vitamin B 12

Aim of the study was to clarify the relationship between metformin-induced vitamin B12 (B12) deficiency, hyperhomocysteinemia and vascular complications in patients with type 2 diabetes. Serum B12 concentrations, homocysteine plasma levels, the presence of retinopathy and history of macroangiopathy (stroke or coronary heart disease) were analyzed in patients without renal dysfunction (serum creatinine<115 μmol/L). Firstly, B12 status was analyzed in 62 consecutive metformin-treated patients. Secondly, the relationship between B12, homocysteine and vascular complications was analyzed in 46 metformin-treated and 38 age- and sex-matched non-metformin-treated patients. Among the 62 consecutive metformin-treated patients, B12 was deficient (<150 pmol/L) in 8 (13%) and borderline-deficient (150-220 pmol/L) in 18 (29%): the larger the metformin dosage, the lower the B12 (P=0.02, Spearman's ρ=-0.30). There were independent correlations between metformin use and B12 lowering (P=0.02, r = -0.25), and B12 lowering and elevation of homocysteine (P<0.01, r=-0.34). Elevation of homocysteine was a risk for retinopathy (P=0.02, OR 1.26, 95%CI 1.04-1.52). There was no significant relation between homocysteine and macroangiopathy. Correlation between B12 and homocysteine was stronger in metformin-treated (P<0.01, r=-0.48) than non-metformin-treated (P=0.04, r=-0.38) patients. In ten B12 deficient patients, B12 supplementation (1,500 μg/day) for 2.2±1.0 months with continued use of metformin raised B12 levels: 152±42 and 299±97 pmol/L before and after treatment, respectively (P<0.01). Metformin-induced B12 lowering in diabetes was associated with elevation of homocysteine, and hyperhomocysteinemia was independently related to retinopathy. Metformin-induced B12 deficiency was correctable with B12 supplementation.

Topics: Aged; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Dietary Supplements; Dose-Response Relationship, Drug; Female; Homocysteine; Humans; Hyperhomocysteinemia; Hypoglycemic Agents; Japan; Male; Metformin; Middle Aged; Prevalence; Risk Factors; Severity of Illness Index; Stroke; Vitamin B 12; Vitamin B 12 Deficiency

The associations of serum levels of homocysteine (tHcy), vitamin B(12), and folate with risk of all-cause and coronary heat disease (CHD) mortality is controversial, and the evidence in older adults is limited. The aim of this study was to examine whether serum folate, vitamin B(12), and tHcy independently predict risk of CHD-related and all-cause mortality in older adults.. Serum concentrations of folate, vitamin B(12), and tHcy were determined from blood samples obtained from 3010 Blue Mountains Eye Study participants (1997-99), aged ≥55 years. CHD and all-cause mortality was confirmed using the Australian National Death Index.. Persons in the highest quartile of serum tHcy had increased risk of CHD mortality compared to those in the lowest quartile (multivariable-adjusted hazard ratio, HR, 2.45, 95% CI 1.30-4.62). A significant continuous association was observed between serum tHcy and CHD mortality (HR per SD ( = 4.8 µmol/l) increase in serum tHcy 1.25, 95% CI 1.08-1.45), after multivariable-adjustment. A significant association between folate deficiency and CHD-mortality was found (multivariable-adjusted HR 1.53, 95% CI 1.01-2.29). Hyperhomocysteinaemia (>15 µmol/l) was a significant predictor of all-cause mortality (multivariable-adjusted HR 1.47, 95% CI 1.18-1.83). A significant interaction was observed between hyperhomocysteinaemia and folate deficiency for all-cause and CHD mortality (p for interaction = 0.03 and p for interaction = 0.05, respectively).. Serum tHcy and folate were independent predictors of CHD and all-cause mortality, while vitamin B(12) was not associated. As raised tHcy levels and folate deficiency are associated with poorer lifestyle, changes to a more healthful lifestyle among older adults may minimize the adverse vascular effects of elevated tHcy.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Coronary Disease; Down-Regulation; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; New South Wales; Prognosis; Proportional Hazards Models; Risk Assessment; Risk Factors; Up-Regulation; Vitamin B 12

Topics: Coronary Disease; Dietary Supplements; Folic Acid; Health Behavior; Humans; Nutritional Physiological Phenomena; Nutritional Requirements; Risk Factors; Vitamin B 12; Vitamin B 6

Whether serum homocysteine levels are associated with coronary heart disease (CHD) and the metabolic syndrome (MS) needs investigation in different ethnic groups. These associations and the influence of serum folate and vitamin B(12) thereupon were addressed separately in genders.. A random sample of Turkish adults was studied cross-sectionally.. Median age of 338 men and 342 women was 55 years. Geometric mean serum homocysteine concentrations were 12.7+/-1.5 micromol/l in men and 9.6+/-1.4 micromol/l in women (p<0.001). Linear regression analysis among 11 variables revealed male sex, reduced estimated glomerular filtration rate (eGFR) and vitamin B(12), (in men) reduced folate as significant independent covariates of higher homocysteine levels. Logistic regression analysis disclosed that (sex-specific) top versus bottom homocysteine tertile was borderline significantly and independently associated with CHD in men and both genders combined, after adjustment for gender, age, smoking status, systolic blood pressure, eGFR, folate and vit B(12). Folate revealed significant inverse association with CHD likelihood in men and combined genders (OR 0.73 for doubling [95%CI 0.56; 0.94]), independently of homocysteine levels and even of presence of type-2 diabetes. Serum vit B(12) concentrations were significantly associated with MS likelihood in women alone after adjustment for sex, age, smoking status, folate and antidiabetic medication.. High serum homocysteine and low folate levels are associated in Turkish men independently with CHD, which needs confirmation in a larger sample. In women, vitamin B(12) concentrations are significantly associated with MS likelihood.

Topics: Adult; Coronary Disease; Cross-Sectional Studies; Female; Folic Acid; Homocysteine; Humans; Linear Models; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Sex Factors; Turkey; Vitamin B 12

Proper absorption of vitamin B12 requires gastric corpus mucosa that functions appropriately and secretes intrinsic factor needed as an essential cofactor for the absorption of dietary vitamin B12 in the small bowel. Here we describe the prevalence of vitamin B12 deficiency and atrophic corpus gastritis (ACG) in patients with coronary heart disease. Fasting serum was obtained from patients who were admitted for cardiovascular diseases at the Coronary Care Unit in Nijmegen, the Netherlands. The status of gastric mucosa was assessed by using the serum levels of pepsinogens I and II, gastrin-17, and Helicobacter pylori IgG antibodies and analyzed over vitamin B12 level subgroups. The study population consisted of 376 patients (mean age, 65 years [SD, 13 years], 227 [60%] males). Low vitamin B12 levels (<150 pM) were detected in 28 patients (7%). Of these 28 patients, 5 (18%) had ACG according to the biomarker assays. Altogether, another 140 patients (37%) had vitamin B12 levels between 150 and 250 pM, of whom 10 (7%) had ACG. Of the remaining patients, five (2%) had ACG. Deficiency of vitamin B12 is common among subjects with coronary heart disease. Up to 20% of these deficiencies are related to ACG.

Topics: Aged; Biomarkers; Coronary Disease; Enzyme-Linked Immunosorbent Assay; Female; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Pepsinogens; Retrospective Studies; Vitamin B 12

Topics: Age Factors; Antipsychotic Agents; Autonomic Nervous System; Cholinergic Antagonists; Comorbidity; Confounding Factors, Epidemiologic; Coronary Disease; Depressive Disorder; Electrocardiography; Heart Rate; Humans; Research Design; Vitamin B 12

Homocysteine and possibly also folate and vitamin B(12) are involved in the pathogenesis of cardiovascular disease. We investigated the prevalence of hyperhomocysteinemia in patients with coronary heart disease (CHD), as well as folate and vitamin B(12), the main nutritional factors determining the level of homocysteine.. Patients with angiographically documented CHD were prospectively investigated (n = 315, 70% male, mean age 61 [range 36-81] years). Fasting total serum homocysteine was determined by high-performance liquid chromatography and fluorescence detection. Folic acid and vitamin B12 were measured with AxSYMR Systems.. Median homocysteine concentrations for homocysteine, folate and vitamin B12 were 12.8 micromol/l, 6.8 ng/ml and 345 pg/ml, respectively. Homocysteine levels >10 micromol/l were found in 82% of men and 73% of women. In 19% of the patients serum folate was <3 ng/ml and 22% of the patients had serum vitamin B12 values <250 pg/ml. In a multivariate linear regression model, folate and vitamin B(12) showed significant negative correlations to homocysteine, explaining 5 and 3% of its variability. Age and creatinine were the most important determinants for serum homocysteine, contributing 12 and 7%, respectively.. The main determinants of total homocysteine in patients with CHD are higher age and increased creatinine. The association of lower levels of folate and vitamin B12 with higher levels of homocysteine may indicate poor dietary habits in these patients.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Chromatography, High Pressure Liquid; Coronary Disease; Creatinine; Diet; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Linear Models; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Vitamin B 12; Vitamin B Complex

A biomarker profile of high folate and vitamin B-12 and low plasma homocysteine concentrations reduces the risk of coronary heart disease (CHD) and may be linked to diet. The objectives of the present study were to identify a food pattern related to these biomarkers and to examine its association with CHD risk. Dietary patterns related to biomarker plasma concentrations were constructed from data obtained in the Coronary Risk Factors for Atherosclerosis in Women (CORA) Study (200 cases; 255 controls) using the reduced rank regression statistical method. Risks for CHD with relation to the identified pattern were estimated in the CORA study and in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study with 157 cases of incident myocardial infarction among 26,795 participants. In these 2 German study populations, whole-grain bread, fresh fruit, olive oil, mushrooms, cruciferous vegetables, wine, and nuts contributed the most positively and fried potatoes the most negatively to a dietary pattern that was directly associated with both plasma folate and vitamin B-12 concentrations, but inversely with plasma homocysteine. Multivariate-adjusted relative risks for CHD across increasing quintiles of the food pattern score were 1.0, 0.55, 0.52, 0.58, 0.39 (P for trend = 0.05) in the case-control sample and 1.0, 0.95, 0.75, 0.56, 0.72 (P for trend = 0.041) in the prospective study. The combination of a high intake of whole-grain bread, fresh fruit, olive oil, mushrooms, cruciferous vegetables, wine, and nuts with a low intake of fried potatoes was associated with a favorable biomarker profile of homocysteine metabolism and reduced risk of CHD.

Topics: Aged; Body Mass Index; Case-Control Studies; Coronary Disease; Diet; Female; Folic Acid; Germany; Homocysteine; Humans; Middle Aged; Multivariate Analysis; Risk Factors; Vitamin B 12

The cases of hyperlipoproteinemic secondary type IV are manifested by elevation of triglycerides, with normal or high cholesterol and lightly high homocysteine. The effect of vitamins B12, B6 and folic acid, on homocysteine and lipids, in 24 male patients, 35-68 years, with hiperlipoproteinemia secondary type IV with myocardial isquemic, and without previous treatment of hipolipemiant, was investigated. The patients were supplemented with therapeutic doses tablets of vitamin B12, 500 (microg/day); B6, (600 mg/day) and folic acid (20 mg/ day), during 120 days. Homocysteine, triglycerides, total and fractional cholesterol, at (basal), 30, 60, 90 and 120 days, were determined. Descriptive statistical analyses were applied, coefficient of correlation of Pearson and proves of "t", with a p < 0.005; the data were processed by statistical program SPSS version 8.0. The results showed a decrease in the levels of homocysteine from basal 17.1 +/- 0.7 micromol/L to 13.18 +/- 0.83 micromol/L, at the end of experimental period. The triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), very low density lipoprotein (VLDL) showed a reduction of (21.8 mg/dl; 8.5 mg/dl; 5.87 mg/dl; respectively) for every pmol/L of reduced homocysteine, with (p < 0.001) for triglycerides. High density lipoprotein (HDL) increased 1.1 mg/dl and coronary risk descent in 24%. We concluded that therapeutic doses of vitamins B12, B6 and folic acid, may is effective in decreased plasmatic homocysteine levels and lipids, mainly triglycerides, with a reduction of coronary risk, to these type of patients, with not collateral effects of neuropathy

Topics: Adult; Aged; Biomarkers; Cholesterol, HDL; Coronary Disease; Folic Acid; Homocysteine; Humans; Hyperlipoproteinemia Type IV; Lipids; Lipoproteins, LDL; Male; Middle Aged; Risk Factors; Triglycerides; Vitamin B 12; Vitamin B 6; Vitamin B Complex

High serum total homocysteine (tHcy) and lipoprotein (a) [Lp(a)] levels are independent risk factors for cardiovascular disease. In this study, we examined the relationship of tHcy and Lp(a) levels with the components of metabolic syndrome. Fifty-one patients diagnosed with metabolic syndrome (median age: 38 [range 25-48] years) and 50 healthy subjects (median age: 35 [26-48] years) were included in the study. We used the National Cholesterol Education Program criteria to define metabolic syndrome. Total tHcy concentrations were measured by using an IMX (Abbott Diagnostics, Abbott Park, IL, USA). Lipoprotein (a) was measured by immunonephelometry using Behring nephrometer method (Behring BN 100, Behring, Germany). Total homocysteine and Lp(a) levels were found to be higher in the metabolic syndrome group than in the control group (tHcy: 24.2 vs 13.4 micromol/l, P < 0.01 and Lp(a): 34.9 vs 15.8 mg/dl, P < 0.01). Vitamin B12 levels were lower in the metabolic syndrome group than in the control group (214 pg/ml vs 247 pg/ml, P < 0.01). In partial correlation, tHcy and Lp(a) concentrations were unrelated to metabolic syndrome or to the components of metabolic syndrome, including fasting serum triglycerides, HDL-cholesterol, fasting glucose, blood pressure, or body mass index. tHcy levels were strongly related only to the vitamin B12 concentration. The risk of cardiovascular disease is higher in patients with metabolic syndrome compared with the normal population. High tHcy and Lp(a) levels should be evaluated in this group of patients in addition to the evaluation of the parameters of metabolic syndrome.

Topics: Adult; Coronary Disease; Female; Folic Acid; Homocysteine; Humans; Insulin Resistance; Lipoprotein(a); Male; Metabolic Syndrome; Middle Aged; Reference Values; Risk Factors; Statistics as Topic; Turkey; Vitamin B 12

Thromboembolic disease is a major cause of morbidity and mortality in many countries. Our previous study found that Chinese subjects carried the same polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene as described in Western studies. The aim of the present study was to determine the influence of MTHFR polymorphism, B vitamins and other factors on plasma homocysteine (Hcy) levels and risk of thromboembolic disease in Chinese.. One hundred and six subjects were enrolled into the study. They were categorized into 4 groups: healthy individuals (n = 42); those with diabetes mellitus (n = 20); those with deep vein thrombosis (DVT) (n = 11); and those with coronary artery disease (CAD) (n = 33). Plasma levels of folic acid, vitamins B6 and B12, Hcy, and fasting blood sugar were measured; total cholesterol, triglycerides, complete blood count, and 677 C-->T mutation in MTHFR were determined.. Plasma Hcy was lowest in the healthy subjects, higher in diabetics, followed by patients with DVT, and highest in patients with CAD (p < 0.001, ANOVA). MTHFR C677T polymorphism was the common factor affecting plasma logHcy levels in all 4 groups of subjects. Triglycerides affected plasma logHcy in the CAD patients. For the 4 groups as a whole, MTHFR polymorphism, triglycerides, and vitamin B12 were the most significant factors influencing plasma Hcy.. We suggest that high plasma Hcy is an important risk factor for CAD. Other factors including MTHFR polymorphism, vitamin B12, triglycerides, total cholesterol, and gender might affect Hcy levels in different diseases and conditions.

Topics: Adult; Aged; Aged, 80 and over; Coronary Disease; Female; Folic Acid; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Polymorphism, Genetic; Risk Factors; Thromboembolism; Vitamin B 12; Vitamin B 6

The main objective of our study was to determine and compare total serum homocysteine (tHcy) levels among tri-ethnic college students. The 180 tri-ethnic subjects completed Cardiovascular Risk Assessment questionnaires, and gave 15 mL fasting blood for serum tHcy and blood lipid analysis. The mean tHcy (+/- SD) of the all subjects was 6.33 +/- 3.15 micromol/L. Male subjects had significantly (P=.001) higher serum tHcy levels compared with female subjects. Black non-Hispanic females and Hispanic females showed significantly (P=.003) lower tHcy levels than White non-Hispanic females. Moderate elevations of tHcy levels were strongly related to cigarette smoking, physical inactivity, behavioral style, high blood pressure, and low intakes of folate, and vitamins B6 and B12. A positive association of tHcy levels with cardiovascular heart disease (CHD) risk point standards was observed in females (P=.001), Hispanic (P=.001), Hispanic males (P=.049), Hispanic females (P=.009), and Black non-Hispanic females (P=.005). We observed gender and ethnic differences in tHcy levels of this young population with normal tHcy levels. Abnormally high tHcy concentrations appear to be acquired later in life.

Topics: Adult; Black or African American; Coronary Disease; Female; Florida; Folic Acid; Hispanic or Latino; Homocysteine; Humans; Hyperhomocysteinemia; Lipids; Male; Risk Factors; Sex Factors; Smoking; Universities; Vitamin B 12; Vitamin B 6; White People

Topics: Adult; Age Factors; Coronary Disease; Exercise; Feeding Behavior; Female; Florida; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Risk Factors; Smoking; Vitamin B 12; Vitamin B 6

Several prospective studies reported that fibrates might increase blood total homocysteine (tHcy). In this study we aimed to establish whether the reported fibrate treatment was associated with an increased risk of mild hyperhomocysteinaemia in patients with clinical coronary heart disease, and to establish whether confounding variables may influence this effect.. A retrospective, case-control analysis.. A total of 410 patients, 301 males and 109 females, mean age 59.2 were examined in a Czech sample from the EUROASPIRE II survey. In addition to examinations and measurements, defined by the protocol, we estimated serum total homocysteine (tHcy), folate, B12 vitamin and methylenetetrahydrofolate reductase (MTHFR) genotypes.. We found significantly higher tHcy concentrations in patients with reported treatment with fibrate (16.6 +.- 0.66 micromol/l) compared with no lipid-lowering treatment (13.5 +/- 0.64 micromol/l, P<0.001) or to statin (12.4 +/- 0.39 micromol/l, P<0.001). Concentrations of tHcy > or =15 mmol/l (i.e. mild hyperhomocysteinaemia) as a dependent variable were positively associated with age (OR 1.18, P<0.0003), serum vitamin B12 (OR 0.87, P<0.003), serum creatinine (OR 1.35, P<0.0001 and treatment with fibrates (OR 1.30, P<0.0001), using multiple regression. Using unifactorial or multifactorial analyses, association between fibrate and tHcy is independent from conventional confounders such as age, gender, smoking, folate or B12 concentration, serum creatinine and MTHFR genotypes, however interference of low folate or B12 and fibrate treatment resulted in concentrations of tHcy more than 20 micromol/l.. Fibrate treatment was associated with a significant increase in prevalence of the risk of mild hyperhomocysteinaemia in coronary patients, independently from conventional confounders.

Topics: Case-Control Studies; Coronary Disease; Creatinine; Female; Folic Acid; Genotype; Homocysteine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperhomocysteinemia; Hypolipidemic Agents; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Prevalence; Retrospective Studies; Vitamin B 12

Topics: Angioplasty, Balloon, Coronary; Coronary Disease; Coronary Restenosis; Drug Therapy, Combination; Folic Acid; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperhomocysteinemia; Platelet Aggregation Inhibitors; Risk Factors; Stents; Vitamin B 12; Vitamin B 6

Hyperhomocysteinemia, associated with low folate and low B12 levels, is known to be an independent risk factor for atherosclerosis. Only a few available data has been demonstrated in Thai patients.. To evaluate serum fasting homocysteine, folate and B12 levels whether to see they are associated with coronary artery disease (CAD).. Three hundred and one consecutive suspected CAD patients who underwent coronary angiography at the Police General Hospital were studied. The mean age of the patients, 195 males and 106 females, was 63.0 +/- 10.0 year (range 39-85). A total of 218 patients were angiographically demonstrated as having CAD. The mean serum homocysteine level of CAD patients had a non significant higher level than those of 83 non CAD patients: 11.4 +/- 6.2 vs 10.2 +/- 4.2 umol/L, p = 0.06. Means of folate and B12 level in the CAD patients and non CAD patients were 6.6 +/- 4.6 vs 7.0 +/- 4.3 nmol/L, p = 0.49 and 650.9 +/- 415.4 vs 613.3 +/- 443.2 pmol/L, p = 0.56 respectively. No significant correlations were found between homocysteine with folate and B12 levels. Logistic regression analysis showed a significant association between homocysteine and CAD with OR = 1.08 (95%CI, 1.01-1.16), p = 0.03 after being adjusted for age, sex, DM, HT history of hyperlipidemia, smoking, BMI, folate and B12 levels. No significant association between homocysteine level with the number of coronary vessel stenosis, age, BMI, DM, HT smoking and history of hyperlipidemia was observed in the present study.. Hyperhomocyteinemia, but not folate and B12 levels, may be an independent risk factor for coronary artery disease in Thai patients.

Topics: Coronary Disease; Cross-Sectional Studies; Female; Homocysteine; Humans; Logistic Models; Male; Seroepidemiologic Studies; Thailand; Vitamin B 12

To test the hypothesis that the incidence of fatal coronary heart disease and cardiovascular disease in a general population is related to serum and red cell folate and vitamin B-12 concentrations.. Cohort study with follow up of 29 years.. Busselton, Western Australia.. 1419 men and 1531 women aged 20 to 90 years, who were alive more than three years after their participation in the 1969 Busselton health survey. 2314 (78.4%) had no cardiovascular disease at the initial survey.. Hazard ratios for fatal coronary heart disease and cardiovascular disease in men and women according to baseline concentrations of serum and red cell folate and serum vitamin B-12.. 213 men and 159 women died from coronary heart disease, and 342 men and 302 women died from cardiovascular disease. Serum and red cell folate concentrations showed a moderate positive correlation (r=0.26, P<0.001) but otherwise serum and red cell folate and serum B-12 concentrations were not strongly correlated with each other or with other standard risk factors. After age and standard risk factors were adjusted for, there was no independent association between folate and B-12 concentrations and death from coronary heart disease or cardiovascular disease in the full cohort or the subcohort with no cardiovascular disease at baseline. The multivariate adjusted hazard ratio for death from cardiovascular disease in the lowest versus the highest category of red cell folate concentration was 1.05 (95% confidence interval 0.77 to 1.43) in men and 1.10 (0.81 to 1.51) in women.. These findings do not support the hypothesis that lower folate and B-12 concentrations increase the risk of fatal cardiovascular disease in a general population. The routine use of these vitamins for preventing cardiovascular disease should await evidence from clinical trials.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Cohort Studies; Coronary Disease; Erythrocytes; Female; Folic Acid; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Multivariate Analysis; Prognosis; Risk Factors; Survival Analysis; Vitamin B 12; Western Australia

Elevated plasma homocysteine levels have been associated with increased risk of cardiovascular disease. A 2756A>G polymorphism has been found in the gene (MTR) coding for methionine synthase, an enzyme catalyzing remethylation of homocysteine to methionine.. In a Dutch case-control study comprising 123 cases with coronary heart disease (CHD) and 540 controls, we evaluated whether the MTR 2756A>G polymorphism was associated with plasma homocysteine, vitamin B12, folate concentrations, and CHD risk.. The polymorphism was not associated with fasting or post-methionine load homocysteine concentrations. Individuals with the GG genotype had 30% lower vitamin B12 concentrations than individuals with AA or AG genotype (P < 0.05). After adjustment for CHD risk factors, the odds ratio (OR) of CHD was 4.0 (95% CI 1.4-11.6) for the GG genotype and 0.7 (95% CI 0.4-1.2) for the AG genotype, when compared to the AA genotype. In conclusion, despite the absence of an association with plasma homocysteine, the GG genotype represented a four-fold increased risk of CHD when compared to the AA genotype. Before putting effort in additional epidemiological studies, it needs to be established first whether this polymorphism has functional consequences for enzyme activity.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Adenine; Case-Control Studies; Coronary Disease; Folic Acid; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Genotype; Guanine; Homocysteine; Humans; Middle Aged; Osmolar Concentration; Risk Factors; Vitamin B 12

The serum/plasma total homocysteine (tHcy) concentration, now recognized as an independent risk factor for accelerated atherosclerotic disease, is increased in overtly hypothyroid patients, and it decreases with thyroid replacement therapy. Whether or not individuals with subclinical hypothyroidism also increase their tHcy concentrations, and whether this elevation might help to explain the increased prevalence of the atherosclerotic diseases observed in this condition, remains unclear. If individuals with subclinical hypothyroidism have higher tHcy concentrations than euthyroid subjects, there would be added incentive to treat this condition earlier. In this cross-sectional study (New Mexico Elder Health Survey) of a randomly selected sample of Medicare recipients (age > or =65 years), no significant difference in serum tHcy concentrations could be detected between the 112 participants with subclinical hypothyroidism (Groups 2 and 3) and the 643 participants with thyrotropin (TSH) values < or =4.6 microU/mL (Group 1) after adjusting for differences in gender, ethnicity, age, and serum concentrations of folate, vitamin B(12), and creatinine. Only those participants with the highest TSH levels (>10 microU/mL) (Group 3) had a significantly higher prevalence of coronary heart disease (CHD) when compared against Group 1 participants (p = 0.007). No consistent significant differences in the prevalences of CHD or in the CHD risk factors examined were observed when all participants with subclinical hypothyroidism (Groups 2 and 3 combined) were compared against Group 1 participants.

Topics: Aged; Aged, 80 and over; Coronary Disease; Creatinine; Fasting; Female; Folic Acid; Health Surveys; Homocysteine; Humans; Hypothyroidism; Male; New Mexico; Prevalence; Risk Factors; Vitamin B 12

This study was performed to determine the effect of homocysteine-lowering therapy (HLT) on endothelium-dependent vasodilation (EDD) and exercise performance in patients with coronary artery disease.. Among the patients who were on the waiting list for coronary intervention, 26 male patients (plasma homocysteine (Hcy) levels > 15 micromol/l) who had a focal stenosis of at least 70% in the left anterior descending artery were included in the study. The patients were matched to receive HLT (n = 15; 0.4 mg of folic acid, 2 mg vitamin B6 and 6 microg of vitamin B12) or placebo (n = 11) until the coronary intervention was performed (mean 3.8 +/- 0.9 weeks). Brachial artery vasomotion test and treadmill stress testing were performed at baseline and 4 weeks after HLT before the time of coronary intervention in each patient. Hcy levels were found to be decreased significantly after HLT compared to baseline (23.4 +/- 6 vs. 11.3 +/- 4 micromol/l; p < 0.001) whereas placebo had no effect. HLT but not placebo produced a marked improvement in EDD, from 3.9 +/- 1.1% to 9.4 +/- 2.3% (p < 0.0001). Endothelium-independent nitroglycerin-induced dilation was similar in the HLT and placebo groups compared with the baseline. In the exercise testing, HLT resulted in a significant improvement in exercise duration and reduction in the amount of maximal ST-segment depression, (from 6.5 +/- 2 to 6.9 +/- 2 min, p = 0.02 and from 1.2 +/- 0.7 to 0.8 +/- 0.5 mm, p = 0.01, respectively) whereas placebo did not.. Lowering Hcy levels improves EDD and exercise performance while reducing the exercise-induced myocardial ischaemia in patients with coronary heart disease and hyperhomocysteinaemia.

Topics: Aged; Analysis of Variance; Blood Flow Velocity; Brachial Artery; Coronary Angiography; Coronary Disease; Double-Blind Method; Drug Therapy, Combination; Endothelium, Vascular; Exercise Test; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Prospective Studies; Ultrasonography; Vasodilation; Vitamin B 12; Vitamin B 6

The screening and therapeutic guidelines for the management of lipid abnormalities are reasonably well established. However, other risk factors like hyperhomocysteinemia (HCA) and single nucleotide polymorphisms involving the angiotensin converting enzyme (ACE) and angiotensinogen genes, various clotting factors etc., have yet to be established firmly as other causative factors of atherothrombotic disease. Our study was aimed at finding the relationship between HCA, folate, vitamins B12 levels, and mutations in the 5,10-methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS) genes.. We studied 230 subjects, which included patients with angiographically documented coronary heart disease (CHD) (n=115) and controls (n=115) with no history of CHD.. Elevated levels of plasma homocysteine, above 18 nmoles/ml, were detected in 19.13% and 18.26% of our patients and controls, respectively. Homocysteine was significantly correlated to Apo A1 (r=0.51, p < 0.05) and Apo B (r=0.49, p < 0.05). The heterozygous MTHFR mutation was found to be 54.5% (12/22) in our patients with HCA. Of these, 31.8% (7/22) were deficient for plasma folate. Heterozygosity for T833C mutation in the CBS gene was observed in 9.99% (2/22) of our patients with HCA. Both these patients were also deficient for plasma folate and vitamin B12.. In our study, heterozygosity for the thermolabile MTHFR mutation was found to be associated with hyperhomocysteinemia (HCA). This genetic predisposition to HCA could be risk factor for CHD and can be correlated with vitamin supplementation. To the best of our knowledge this is the first report from India on plasma homocysteine levels and its genetic aspect in patients with CHD.

Topics: Adult; Coronary Disease; Cystathionine beta-Synthase; Female; Folic Acid; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Oxidoreductases Acting on CH-NH Group Donors; Risk Factors; Vitamin B 12

Homocysteine is associated with coronary disease (CAD). However, the strength of the association after accounting for traditional and emerging risk factors is unclear, particularly since flour fortification with folate was mandated in the USA. We analyzed the association between traditional and emerging risk factors and CAD in 504 patients undergoing clinically-indicated angiography between July 1998 and January 1999. Significant CAD (> or =50% stenosis in > or =1 artery) was present in 271 patients (54%). Mean homocysteine (micromol/l) was 9.36+/-3.07; hyperhomocysteinemia (>13 micromol/l) was present in 7.9% of patients. Mean homocysteine was 9.29+/-3.02 in patients with no disease (no stenoses or stenoses <10%), 9.09+/-2.47 in patients with mild disease (stenoses 10-50%), 9.12+/-2.39 in patients with one vessel disease (VD) (>50% stenosis in one coronary artery), 9.28+/-3.19 in patients with two VD, and 10.1+/-3.89 in patients with three VD (P=0.0793). Multivariate analysis that included age, gender, smoking, LDL, HDL, Lp(a), apo A1, and apo B revealed no independent association between quartile of homocysteine and odds ratio (OR) for CAD. In summary, we found no association between homocysteine and CAD on angiography. The homocysteine-lowering effect of folate-fortified flour, or the inclusion of many traditional and emerging risk factors in multivariate analysis, are potential explanations.

Topics: Adult; Aged; Coronary Angiography; Coronary Disease; Edible Grain; Female; Folic Acid; Food, Fortified; Homocysteine; Humans; Male; Middle Aged; Risk Factors; Severity of Illness Index; Vitamin B 12

Homocysteine (Hcy) is an independent risk factor for coronary artery disease, but there are no reports on Hcy levels in patients undergoing coronary artery bypass graft (CABG) surgery. Interactions between Hcy and copper may mediate the vasculopathic impact of Hcy, and this may play a role in vein graft failure. The aim of this study was to assess the perioperative levels of Hcy, copper, ceruloplasmin (CP), folate, and vitamin B12 in patients undergoing myocardial revascularization surgery.. Blood samples were taken from 55 consecutive patients undergoing elective conventional CABG (43 male; mean age, 63.2 +/- 5.2 years) 1 day preoperatively and postoperatively at 1 day, 6 days, and 6 weeks. Hcy, copper, CP, red cell folate, vitamin B12, creatinine, and C-reactive protein (CRP) were then measured using standard clinical chemistry methods. The same protocol was applied to 10 patients (7 male; mean age, 63.3 +/- 5.2 years) undergoing off-pump coronary artery bypass (OPCAB) surgery.. In the conventional CABG group, there were significant increases in the plasma concentrations at 6 days and 6 weeks postoperatively of Hcy (from 10.1 to 11.6 and 13.5 micromol/L, respectively), plasma copper (from 13.5 to 20.3 and 18.5 micromol/L), and serum ceruloplasmin (from 0.3 to 0.41 and 0.44 g/L). CRP and vitamin B12 were elevated at 6 days but not 6 weeks after the operation. In contrast, red cell folate and creatinine were not significantly changed. The subgroup analysis for the OPCAB patients showed the same trend as for the conventional group.. Coronary surgery precipitates a significant and sustained increase in the blood concentrations of Hcy and copper, which is not due to a decrease in folate and vitamin B12, altered renal function, or inflammation. Further studies are required to establish whether the concomitant increase in Hcy and copper plays an etiological role in vein graft disease.

Topics: Aged; Cardiopulmonary Bypass; Ceruloplasmin; Copper; Coronary Artery Bypass; Coronary Disease; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Minimally Invasive Surgical Procedures; Postoperative Complications; Risk Factors; Vitamin B 12

Coronary in-stent restenosis represents a clinical problem. Because homocysteine is being discussed as a new risk factor for atherosclerosis and thrombosis, this study investigated the relations of homocysteine, folate, and vitamin B(12) to the rate of in-stent restenosis. Patients undergoing successful percutaneous transluminal coronary angioplasty of native coronary lesions with stent implantation were investigated for fasting total serum homocysteine, folic acid, and vitamin B(12). The rate of in-stent restenosis was determined angiographically after 6 months, or earlier if clinically indicated. Of 292 enrolled patients, 262 (90%) (189 men and 73 women) underwent control angiography on an average of 6.3 +/- 1.0 (SD) months after intervention. The rate of in-stent restenosis was 36%. Univariate and multivariate analyses revealed no significant differences between patients with or without restenosis with regard to total homocysteine (median [interquartile range]: 12.9 [11.2 to 14.8] and 12.4 [10.3 to 15.4] micromol/L, respectively), folate (16.1 [12.4 to 20.5] and 15.4 [12.5 to 19.5] nmol/L, respectively), or vitamin B(12) (239.0 [182.5 to 322.1] and 258.4 [205.8 to 330.5] pmol/L, respectively). These results suggest that homocysteine, folate, and vitamin B(12) are not related to the angiographically determined rate of coronary in-stent restenosis after 6 months.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Disease; Coronary Restenosis; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Risk Factors; Stents; Vitamin B 12

As an important risk factor for coronary atherosclerosis, elevated plasma total homocysteine (t-hcy) concentration has recently received greater attention than have conventional risk factors. Though less reactive than homocysteine, cysteine (cys) is the most abundant plasma thiol and may function as an extracellular regulating factor of thiol/disulfide exchange in order to maintain an adequate redox status. An increase in the total amount of this compound may be noxious depending on environmental conditions. In the present study, the aim was to investigate changes of plasma total cysteine, homocysteine and other determinants in different types of coronary heart disease.. Plasma total homocysteine (t-hcy), cysteine (t-cys), cysteinylglycine (t-cysgly), folic acid, vitamin B(12), lipid parameters, total protein, albumin and creatinine levels were studied in plasma from 68 patients with coronary heart disease and 42 healthy controls. After reduction of disulfide bonds with tri-n-buthylphosphine, plasma total thiols were assayed using high performance liquid chromatography (HPLC) and fluorescence detection following derivatization of sulfhydryl groups with 7-fluoro-benzo-2-oxa-1,3-diazole-4-sulfonate (SBD-F). Other parameters were determined by using commercial kits.. Plasma t-hcy and t-cys levels were higher in patients (P<0.0001) than in controls, but t-cysgly was unchanged. Hcy and cys levels were correlated with age in the whole study population (r=0.49, r=0.46, P<0.01). Plasma t-hcy positively correlated with plasma t-cys (r=0.53, P<0.01) and t-cysgly (r=0.49, P<0.01) in patients, and with plasma t-cys (r=0.57, P<0.01) in controls. Postmenopausal women had higher t-cys and t-hcy levels than premenopausal women among the controls (P<0.01). Folate and vitamin B(12) levels were similar in both patients and controls. Patients with vitamin B(12) levels below normal had higher plasma t-cys and t-cysgly levels (P<0.05). Interestingly, control subjects with lower vitamin B(12) levels had lower plasma t-hcy levels (P<0.05). Plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, total protein, albumin and creatinine levels in patients and controls were within the normal range, but only HDL-cholesterol levels in patients were lower than in controls (P<0.0001). Triglyceride and VLDL levels of patients were also higher than those of controls (P<0.0001).. Higher plasma total cysteine levels are as important as higher plasma total homocysteine levels. Both parameters are intercorrelated and may act synergistically. To discern their respective roles in atherosclerotic disease, these aminothiol levels have to be considered together.

Topics: Aged; Case-Control Studies; Coronary Disease; Cysteine; Dipeptides; Female; Folic Acid; Homocysteine; Humans; Lipoproteins, VLDL; Male; Middle Aged; Risk Factors; Triglycerides; Vitamin B 12

Topics: Case-Control Studies; Coronary Disease; Female; Folic Acid; Genotype; Germany; Homocysteine; Humans; Logistic Models; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Prevalence; Risk Factors; Vitamin B 12

Fortification of enriched cereal grain flour products with folic acid has drastically reduced the prevalence of deficient plasma folate status, a major determinant of plasma total homocysteine (tHcy) levels. We hypothesized that even more liberally defined "suboptimal" plasma folate status might no longer contribute importantly to the population attributable risk (PAR) for mild hyperhomocysteinemia, a putative atherothrombotic risk factor. We determined fasting plasma tHcy, folate, vitamin B(12), and pyridoxal 5'-phosphate levels, along with serum creatinine and albumin levels, in 267 consecutive patients (aged 61+/-9 [mean+/-SD] years, 76.4% men and 26.6% women) with stable coronary artery disease (CAD) who were nonusers of vitamin supplements or had abstained from supplement use for at least 6 weeks before examination. Subjects were evaluated a minimum of 3 months after the implementation of flour fortification was largely completed. Relative risk estimates for the calculation of PAR were derived from a multivariable-adjusted logistic regression model with >/=12 micromol/L tHcy as the dependent variable and with age, sex, pyridoxal 5'-phosphate (continuous), albumin (continuous), <5 ng/mL folate, <250 pg/mL vitamin B(12), and >/=1.3 mg/dL creatinine as the independent variables. The prevalence of >/=12 micromol/L plasma tHcy was 11.2% (30 of 267 patients). PAR estimates (percentage) for >/=12 micromol/L tHcy were as follows: <5 ng/mL folate (<1%), <250 pg/mL vitamin B(12) (24.5%), and >/=1.3 mg/dL creatinine (37.5%). In the era of folic acid-fortified cereal grain flour, renal insufficiency and suboptimal vitamin B(12) status (but not folate status) contribute importantly to the PAR for mild hyperhomocysteinemia among patients with stable CAD.

Topics: Adult; Aged; Coronary Artery Disease; Coronary Disease; Creatinine; Edible Grain; Female; Flour; Folic Acid; Food, Fortified; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Renal Insufficiency; Risk Factors; Vitamin B 12

Although several prospective studies have shown that low folate intake and low circulating folate are associated with increased risk of coronary heart disease (CHD), the findings are inconsistent.. We studied the associations of dietary intake of folate, vitamin B(6), and vitamin B(12) with the risk of acute coronary events in a prospective cohort study of 1980 Finnish men 42 to 60 years old examined in 1984 to 1989 in the Kuopio Ischemic Heart Disease Risk Factor Study. Nutrient intakes were assessed by 4-day food record. During an average follow-up time of 10 years, 199 acute coronary events occurred. In a Cox proportional hazards model adjusted for 21 conventional and nutritional CHD risk factors, men in the highest fifth of folate intake had a relative risk of acute coronary events of 0.45 (95% CI 0.25 to 0.81, P=0.008) compared with men in the lowest fifth. This association was stronger in nonsmokers and light alcohol users than in smokers and alcohol users. A high dietary intake of vitamin B(6) had no significant association and that of vitamin B(12) a weak association with a reduced risk of acute coronary events.. The present work in CHD-free middle-aged men is the first prospective cohort study to observe a significant inverse association between quantitatively assessed moderate-to-high folate intakes and incidence of acute coronary events in men. Our findings provide further support in favor of a role of folate in the promotion of good cardiovascular health.

Topics: Acute Disease; Adult; Analysis of Variance; Clinical Trials as Topic; Cohort Studies; Coronary Disease; Diet; Dose-Response Relationship, Drug; Finland; Folic Acid; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Prospective Studies; Pyridoxine; Risk Factors; Vitamin B 12

Insulin resistance, associated metabolic abnormalities, and elevated homocysteine levels are risk factors for cardiovascular disease (CVD). We examined relationships between homocysteine levels and features of insulin resistance syndrome (IRS).. We measured clinical characteristics, plasma levels of fasting homocysteine, folate, B vitamins, creatinine, and fasting and 2-h insulin and glucose levels after a 75-g oral glucose tolerance test in 2,214 subjects without CVD at the fifth examination (1991-1995) of the Framingham Offspring Study. After excluding 203 subjects with diabetes, the remaining 2,011 subjects were categorized as having none, one, two, or all three of the phenotypes of IRS: impaired glucose tolerance, hypertension, and/or a central metabolic syndrome (two or more traits: obesity, dyslipidemia, or hyperinsulinemia). In addition, in 1,592 subjects attending the sixth examination (1995-1998), we measured the urine albumin/creatinine ratio (UACR). Age-, sex-, creatinine-, vitamin-, and UACR-adjusted mean homocysteine levels or proportions with homocysteine >14 micromol/l in each phenotypic category and differences between categories were assessed with regression models.. The mean age of the subjects was 54 years (range 28-82); 55% were women, 12.3% had hyperinsulinemia, and 15.9% had two or more of the IRS phenotypes. Adjusted mean homocysteine levels were higher comparing those with hyperinsulinemia (9.8 micromol/l) and those without (9.4 micromol/l, P = 0.04) and were higher among subjects with two or more IRS phenotypes (9.9 micromol/l) compared with those with 1 or no phenotype (9.3 micromol/l, P = 0.003). Mean UACR levels were also higher among subjects with two or more IRS phenotypes (7.2 mg/g) compared with those with 1 or no phenotype (5.5 mg/g, P = 0.007).. Hyperhomocysteinemia and abnormal urinary albumin excretion are both associated with hyperinsulinemia and may partially account for increased risk of CVD associated with insulin resistance. Because hyperhomocysteinemia and microalbuminuria also reflect endothelial injury, these observations also support the hypothesis that endothelial dysfunction is associated with expression of the IRS.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Albuminuria; Blood Glucose; Coronary Disease; Creatinine; Fasting; Female; Folic Acid; Glucose Tolerance Test; Homocysteine; Humans; Insulin; Insulin Resistance; Male; Massachusetts; Middle Aged; Risk Factors; Sex Factors; Vitamin B 12

Hyperhomocysteinemia is an independent risk factor for coronary disease and elevated plasma homocysteine levels have been documented in heart transplant recipients. The aim of this study was to test the hypothesis that homocysteine levels are associated with presence or absence of transplant coronary artery disease.. Forty-three non-smoking adults were recruited, all of whom had received a heart transplant between 2 and 7 yr previously. All 43 had blood drawn for fasting homocysteine level on the day of presentation. All patients had undergone diagnostic coronary angiography within the past 6 months.. For all patients, the average fasting plasma homocysteine level was 17.0+/-SD 6.6 micromol/L with a range from 6.0 to 36.9 micromol/L. Twenty-six patients (60%) had fasting plasma homocysteine levels above 15.0 micromol/L. On the basis of arteriography, patients were categorized as those with angiographically normal (n=22) or abnormal (n=21) coronary arteries. There was no difference in the mean plasma homocysteine level comparing patients with angiographically normal (17.2+/-SD 7.0 micromol/L) to those with abnormal (16.8+/-SD 6.2 micromol/L) coronary arteries. Plasma homocysteine levels increased with increasing plasma creatinine levels (r=0.63, p<0.0001) and with decreasing vitamin B6 levels (r=-0.56, p<0.0001).. Mild hyperhomocysteinemia is a consistent finding among heart transplant recipients. This finding was not associated with transplant coronary artery disease in our patients. The combination of renal dysfunction and vitamin B6 deficiency may explain the unusual prevalence of hyperhomocysteinemia in heart transplant recipients.

Topics: Adult; Aged; Coronary Angiography; Coronary Disease; Creatinine; Cross-Sectional Studies; Female; Heart Transplantation; Homocysteine; Humans; Hyperhomocysteinemia; Linear Models; Male; Middle Aged; Vitamin B 12; Vitamin B 6

Mild to moderate hyperhomocysteinemia is very common among patients undergoing haemodialysis. There is sufficient evidence that hyperhomocysteinemia is an independent risk factor for cardiovascular and or atheromatous disease in end stage renal failure patients. Vitamin supplementation such as vitamin B6, B12 or folate has been proposed to correct this metabolic disturbance and it is to be proved if this intervention benefit these patients, but there is no agreement whether oral folate supplementation is capable to normalize homocysteine levels in end stage renal failure patients.. In 53 patients, undergoing haemodialysis, homocysteine levels (Hcy), folate, vitamin B12, ferritin and C-reactive protein (CRP) were estimated before and after dialysis, without folate supplementation. Thirty voluntary blood donors were used as controls to compare homocysteine levels. After four weeks of oral folate supplementation (10 mg/24 hours) the levels of homocysteine, serum folate and intra-erythrocyte folate were estimated again. Eighteen months later the survival rate of our patients was recorded and analyzed in relation to Hcy and CRP levels.. The results showed that haemodialysis patients exhibited, almost, fourfold higher homocysteine levels than controls (27.39 +/- 11.54 vs 7.38 +/- 3.5, t = -8.2, p = 0.000000). Folate levels, vitamin B12 and CRP increase significantly after haemodialysis where as homocysteine levels decrease (Hcy1 vs. Hcy2: z = 2.08, p = 0.03). Fourteen (14) patients suffered from coronary heart disease (CHD) and they exhibited the higher levels of homocysteine (Hcy1 vs. CHD: z = -3.4, p = 0.0006). All estimations performed revealed a negative correlation between homocysteine levels and plasma or intra-erythrocyte folate. No other variable exhibited any significant influence upon homocysteine levels. After folate supplementation homocysteine levels in the whole number of patients were unchanged (Hcy(before) vs. Hcy(after): 27.39 +/- 11.54 vs. 26.95 +/- 8.22, z = 0.3, p = 0.7, NS). When patients with homocysteine levels higher than 24 micromol/L were selected, a significant decrease was observed (34.77 +/- 9.32 vs. 30.0 +/- 8.05, z = 2.09, p = 0.02). Forty-two patients were treated with erythropoietin for their anemia and we found a positive correlation between C-reactive protein levels and rhu-Epo dose (CRP vs. Epo: r = 0.45, p = 0.002). Homocysteine levels did not exhibit any significant influence upon short-term survival (U = -0.37, p = 0.3, NS) where as CRP levels exhibit a significant influence upon short-term survival (U = 2.15, p = 0.005).. Homocysteine levels in haemodialysis patients are fourfold higher than healthy controls. Folate, vitamin B12 and CRP increases significantly after dialysis. Patients with coronary heart disease exhibit the highest levels of homocysteine. The homocysteine levels are inversely related with the folate levels. The exogenous folate supplementation increase the serum folate levels but decreases homocysteine only in patients with higher than mild hyperhomocysteinemia. Hcy doesn't exert any significant effect upon the short-term survival of the haemodialysis patients but CRP level is a god predictor of the short-term survival of these patients.

Topics: Adult; C-Reactive Protein; Case-Control Studies; Coronary Disease; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Vitamin B 12

Reasons for the increase in mortality due to coronary heart disease (CHD) in UK Indian Asians are not well understood. In this study, we tested the hypotheses that elevated plasma homocysteine concentrations are a risk factor for CHD in Indian Asians, and explain part of their increased CHD risk, compared with Europeans.. We undertook two parallel case-control studies, one in Europeans and one in Indian Asians. We recruited 551 male cases (294 European, 257 Indian Asian) and 1025 healthy male controls (507 European, 518 Indian Asian). Fasting and post-methionine load homocysteine, vitamin B12 and folate concentrations, and conventional CHD risk factors were measured.. Fasting homocysteine concentrations were 8% higher (95% CI 3-14) in cases compared with controls, in both ethnic groups. The odds ratio of CHD for a 5 micromol/L increment in fasting plasma homocysteine was 1.3 (1.1-1.6) in Europeans and 1.2 (1.0-1.4) in Indian Asians. The association between fasting plasma homocysteine and CHD was independent of conventional CHD risk factors in both ethnic groups. Post-load homocysteine concentrations were not significantly different in cases compared with controls. Among the controls, fasting homocysteine concentrations were 6% (2-10) higher in Indian Asians than in Europeans. From the results we estimate that elevated homocysteine may contribute to twice as many CHD deaths in Indian Asians, compared with Europeans. The differences in homocysteine concentrations between the two ethnic groups were explained by lower vitamin B12 and folate levels in Asians.. Plasma homocysteine is a novel and independent risk factor for CHD in Indian Asians, and may contribute to their increased CHD risk. Raised homocysteine concentrations in Indian Asians may be related to their reduced vitamin B12 and folate levels, implying that the increased CHD risk in this group may be reduced by dietary vitamin supplementation.

Topics: Case-Control Studies; Coronary Disease; Europe; Fasting; Folic Acid; Hematinics; Homocysteine; Humans; Hyperhomocysteinemia; India; Male; Middle Aged; Risk Factors; United Kingdom; Vitamin B 12

Topics: Adult; Aged; Asian People; Cardiac Catheterization; Coronary Disease; Female; Folic Acid; Gene Frequency; Homocysteine; Humans; Hyperhomocysteinemia; Korea; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation, Missense; Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Risk Factors; Sex Factors; Vitamin B 12

To examine the hypothesis that the higher rates of coronary heart disease (CHD) in Indians (South Asians) compared with Malays and Chinese is partly attributable to differences in blood concentrations of homocysteine, and related blood concentrations of folate and vitamin B12.. Cross sectional study of the general population.. Singapore.. Random sample of 726 fasting subjects aged 30 to 69 years.. Mean plasma total homocysteine concentrations did not show significant ethnic differences; values were Indians (men 16.2 and women 11.5 mumol/l), Malays (men 15.0 and women 12.5 mumol/l), and Chinese (men 15.3 and women 12.2 mumol/l). Similarly, the proportions with high plasma homocysteine (> 14.0 mumol/l) showed no important ethnic differences being, Indians (men 60.0 and women 21.9%), Malays (men 53.9 and women 37.8%), and Chinese (men 56.6 and women 30.6%). Mean plasma folate concentrations were lower in Indians (men 8.7 and women 10.9 nmol/l) and Malays (men 8.5 and women 10.8 nmol/l), than Chinese (men 9.7 and women 13.8 nmol/l). Similarly, the proportions with low plasma folate (< 6.8 nmol/l) were higher in Indians (men 44.9 and women 36.6%) and Malays (men 45.3 and women 24.5%) than Chinese (men 31.4 and women 12.6%). Mean plasma vitamin B12 concentrations were lowest in Indians (men 352.5 and women 350.7 pmol/l), then Chinese (men 371.1 and women 373.7 pmol/l), and then Malays (men 430.5 and women 486.0 pmol/l).. While there were ethnic differences for plasma folate and vitamin B12 (in particular lower levels in Indians), there was no evidence that homocysteine plays any part in the differential ethnic risk from CHD in Singapore and in particular the increased susceptibility of Indians to the disease.

Topics: Adult; Aged; Biomarkers; China; Coronary Disease; Cross-Sectional Studies; Disease Susceptibility; Female; Homocysteine; Humans; India; Malaysia; Male; Middle Aged; Sex Factors; Singapore; Vitamin B 12

Hyperhomocysteinemia is an important cardiovascular risk factor. Serum homocysteine levels are specially dependent on folate nutritional status. In addition, the oxidative modification of low-density lipoproteins (LDLs) in the endothelial microenvironment is a damaging factor that can be modified with fat-soluble antioxidant vitamins. The present study was done to assess the effect of a supplementation of folic acid and antioxidant vitamins on homocysteine levels and in vitro LDL oxidation in patients with coronary artery disease. Twenty-three patients with angiographically proven coronary artery disease were given supplements for 15 d consisting of one capsule twice a day of a multivitamin preparation containing 0.65 mg folic acid, 150 mg alpha-tocopherol, 150 mg ascorbic acid, 12.5 mg beta-carotene, and 0.4 microgram vitamin B12. Serum lipids, vitamin and homocysteine levels, and in vitro LDL oxidation were measured before and after the supplementation period. During the supplementation period, serum folate levels increased from 5.0 +/- 1.5 to 10.8 +/- 3.8 ng/mL (P < 0.001), vitamin B12 increased from 317.4 +/- 130.4 to 334.5 +/- 123.8 pg/mL (P < 0.05), and alpha-tocopherol increased from 8.2 +/- 5.1 to 13.7 +/- 7.9 mg/L (P < 0.001). Serum homocysteine levels decreased from 8.7 +/- 4.3 to 6.3 +/- 2.2 mumol/L (P < 0.001). In vitro LDL oxidation decreased from 2.6 +/- 1.1 to 1.6 +/- 1.1 nmol malondialdehyde/mg protein (P < 0.001). In comparing patients with healthy controls, basal levels of folate were lower in the patients, whereas vitamin B12, alpha-tocopherol, and homocysteine levels were similar. No changes in serum lipid levels or body weight were observed. In conclusion, a short-term supplementation with folic acid and antioxidant vitamins can reduce serum homocysteine levels and in vitro LDL oxidation in patients with coronary artery disease.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Coronary Disease; Dietary Supplements; Folic Acid; Homocysteine; Humans; Lipid Peroxidation; Lipids; Lipoproteins, LDL; Vitamin B 12; Vitamin E; Vitamins

Homocysteine and vitamins B were correlated with coronary artery disease in patients undergoing diagnostic coronary angiography. 160 patients having > or =1 stenosis (G1), 55 patients having normal coronary arteries (G2) and 171 healthy volunteers (G3) were prospectively recruited. Homocysteine levels were significantly higher in patients, particularly in those with normal coronary angiograms, than in healthy subjects (13.8 +/-6.3 micromol/L in G1 (p < 0.0001) and 15.2 +/- 8.8 micromol/L in G2 (p < 0.0001) versus 10.1 +/- 3.1 micromol/L in G3). Homocysteine levels were not related to the extent of coronary artery disease. In patients with normal angiogram, vitamin B12 and folate levels were significantly higher compared with the other groups (p < 0.05 and p < 0.001, respectively) showing that vitamin B deficiency was not involved in the hyperhomocysteinemia. In conclusion, homocysteine and vitamins B levels do not contribute to discriminate for the presence of coronary artery disease in patients undergoing diagnostic coronary angiography. Homocysteine levels, however, were higher in patients referred for coronary angiography than in healthy controls.

Topics: Aged; Case-Control Studies; Coronary Angiography; Coronary Disease; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Multivariate Analysis; Pyridoxine; Risk Factors; Vitamin B 12

Homocysteine is an intermediate compound formed during metabolism of methionine. The plasma level of homocysteine is dependent on the genetically regulated level of essential enzymes and the intake of folic acid, vitamin B6 (pyridoxine), and vitamin B12 (cobalamine). Elevated serum homocysteine levels are a known risk factor for coronary artery disease (CAD). To establish the magnitude of the CAD that is associated with an increased serum homocysteine level, we compared CAD patients with normal healthy Thai controls.. In a cross-sectional study design we investigated the association between serum homocysteine, vitamin B12 and folate levels and the coronary heart disease in 178 CAD patients and 178 normal healthy controls by age and sex matching. These comprised 266 men and 90 women, mean age 58 +/- 10 years for normal controls and 60 +/- 10 years for CAD patients. Serum homocysteine, vitamin B12 and folate were measured by ELISA method and electrochemiluminescense method respectively.. Paired t-test analysis showed that serum homocysteine concentrations were significantly higher in CAD patients (23.83 +/- 11.29 mumol/L) than in control subjects (19.69 +/- 8.51 mumol/L; p < 0.001). Homocysteine levels were also higher in males than in females. These findings were similar in healthy controls (male: 20.37 +/- 8.5 mumol/L, female: 17.77 +/- 8.2 mumol/L, p < 0.05) and in CAD patients (male: 24.91 +/- 11.8 mumol/L, female: 20.73 +/- 8.9 mumol/L, p < 0.05). Homocysteine above 17 mumol/L occurred more common in CAD patients than in control groups (OR = 1.65, 95% CI = 1.09-2.52, p = 0.0249). Low levels of vitamin B12 and folate did not reaching statistical significance when comparing controls and CAD patients.. Serum homocysteine concentrations were significantly higher in CAD patients than in controls. Serum vitamin B12 and serum folate levels were not statistically significantly different between CAD patients and control groups. The data also demonstrated that the serum homocysteine level is almost always higher in men than in women as previously reported. Although serum vitamin B12 and serum folate levels were not below the upper limit of normal, vitamin B12 and folic acid treatment may reduce serum homocysteine concentrations in CAD patients. We hope that the reversible risk factors will be concern to clinicians for the reduction in the risk of myocardial infarction.

Topics: Aged; Analysis of Variance; Biomarkers; Case-Control Studies; Coronary Disease; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Homocysteine; Humans; Male; Middle Aged; Pteroylpolyglutamic Acids; Reference Values; Sensitivity and Specificity; Thailand; 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

Topics: Coronary Disease; Folic Acid; Hematinics; Homocysteine; Humans; Hyperhomocysteinemia; India; Risk Factors; United Kingdom; Vitamin B 12

Topics: Coronary Disease; Folic Acid; Folic Acid Deficiency; Fructose; Homocysteine; Humans; Hyperhomocysteinemia; India; Malabsorption Syndromes; United Kingdom; Vitamin B 12

A prospective study investigated the association of plasma homocysteine and other risk factors with the incidence of new coronary events at 31 +/- 9 month follow-up in 153 men and 347 women, mean age 81 +/- 9 years. The stepwise Cox regression model showed that significant independent predictors of new coronary events in older persons were age (risk ratio 1.041), plasma homocysteine (risk ratio 1.073), current cigarette smoking (risk ratio 2.524), hypertension (risk ratio 2.032), diabetes mellitus (risk ratio 2.022), serum total cholesterol (risk ratio 1.013), serum high-density lipoprotein cholesterol (risk ratio 0.925), and serum triglycerides (risk ratio 1.004).

Topics: Aged; Aged, 80 and over; Coronary Disease; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Male; Middle Aged; Myocardial Infarction; Recurrence; Risk Factors; Vitamin B 12

The aim of the study was to investigate whether anthropometric and metabolic risk factors for coronary heart disease (CHD) contribute to the variation in homocysteine levels in obese children and adolescents.. A total of 84 children and adolescents were assessed for fasting total homocysteine, methylenetetrahydrofolate reductase polymorphism (C677T mutation), folate and vitamin B12 status, and anthropometric and metabolic risk factors for CHD.. No significant sex differences were found for all available anthropometric and metabolic characteristics except for homocysteine, which was significantly higher in boys than in girls (7.1 vs. 6.3 micromol/l; P<0.05). After adjustment for age and sex, homocysteine correlated significantly with BMI, fat mass, percentage of fat mass, and insulin and showed an inverse correlation with folate levels. Homocysteine did not correlate with vitamin B12; total cholesterol; LDL, HDL, and VLDL; triglycerides; and glucose. BMI and fat mass correlated significantly with insulin and showed a significant inverse correlation with folate. We found no association between homocysteine and the C677T mutation. In multiple regression analyses, insulin was found to be the main correlate of homocysteine.. Our study demonstrates for the first time that insulin is a main correlate of homocysteine in obese children and adolescents and suggests that fat mass-associated hyper-insulinism may contribute to impairment of homocysteine metabolism in childhood obesity

Topics: Adolescent; Blood Pressure; Child; Child, Preschool; Cholesterol; Coronary Disease; Female; Folic Acid; Homocysteine; Humans; Insulin; Lipoproteins; Male; Methylenetetrahydrofolate Reductase (NADPH2); Obesity; Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Regression Analysis; Risk Factors; Triglycerides; Vitamin B 12

Methionine synthase reductase (MTRR) catalyzes the regeneration of methylcobalamin, a cofactor of methionine synthase, an enzyme essential for maintaining adequate intracellular pools of methionine and tetrahydrofolate, as well as for maintaining homocysteine concentrations at nontoxic levels. We recently identified a common A-->G polymorphism at position 66 of the cDNA sequence of MTRR; this variant was associated with a greater than normal risk for spina bifida in the presence of low levels of cobalamin.. To investigate whether the polymorphism was associated with alterations in levels of homocysteine, folate, and vitamin B12, and with risk of developing premature coronary artery disease (CAD), in a population of individuals presenting for cardiac catheterization procedures.. We screened 180 individuals aged < 58 years with angiographically documented coronary-artery occlusions or occlusion-free major arteries for the presence of the 66A-->G MTRR polymorphism using a polymerase-chain-reaction-based assay.. We identified a trend in risk of premature CAD across the genotype groups (P = 0.03) with a sex-adjusted relative risk of premature CAD equal to 1.49 (95% confidence interval 1.10-2.03) for the GG versus AA genotype groups. There was no difference in fasting levels of plasma total homocysteine, serum folate, and vitamin B12 among the three MTRR genotypes.. Our findings suggest that the GG genotype of MTRR is a significant risk factor for the development of premature CAD, by a mechanism independent of the detrimental vascular effects of hyperhomocysteinemia. This association needs to be confirmed in other studies.

Topics: Age Factors; Base Sequence; Coronary Disease; Data Interpretation, Statistical; Female; Ferredoxin-NADP Reductase; Flavoproteins; Folic Acid; Genotype; Homocysteine; Humans; Male; Middle Aged; Molecular Sequence Data; Multivariate Analysis; Polymerase Chain Reaction; Polymorphism, Genetic; Regression Analysis; Risk; Sex Factors; Vitamin B 12

To determine the effects of the thermolabile methylene tetrahydrofolate reductase (MTHFR) mutation on the presence and extent of coronary atherosclerosis in a population with low plasma folate.. 242 consecutive patients undergoing coronary angiography were prospectively evaluated for conventional risk factors, plasma homocysteine, vitamin B-12, and folate, and MTHFR genotype. The severity of coronary atherosclerosis was determined by the Leaman score.. Mean (SD) plasma homocysteine was 15.6 (10) micromol/l in controls and 18.5 (11) micromol/l in patients with coronary artery disease (p > 0.05). Plasma homocysteine concentrations above 15 micromol/l were a risk factor for coronary artery disease (p = 0.03, risk ratio 2.1, 95% confidence interval (CI) 1.07 to 4.4). Homocysteine remained an independent risk factor on multivariate analysis when conventional risk factors were taken into account (p = 0.04). Homocysteine concentrations above 15 micromol/l were correlated with the extent of atherosclerosis (p = 0. 04, risk ratio 3.2, 95% CI 1.3 to 8.2). Homocysteine had no effect on other lipid variables (p > 0.05). Plasma folate was 15.8 (7.2) nmol/l in controls and 11.5 (2.9) nmol/l in patients with coronary artery disease. Plasma folate concentrations below 12.9 nmol/l (5.7 ng/ml) conferred a risk for coronary artery disease (p = 0.03, risk ratio 2.42, 95% CI 1.05 to 5.59). When the MTHFR genotype was determined, the TT genotype was present in 7.4% of patients and 5.2% of controls (p > 0.05). The prevalence of alleles was within the Hardy-Weinberg equilibrium (TT 7, CT 40, CC 53, chi2 = 2.3, p = 0.3). The highest homocysteine concentrations were found in patients with the TT genotype and folate below the median of the population (p = 0. 01). The extent of coronary atherosclerosis judged by the Leaman score was significantly higher in patients with the TT genotype (p = 0.03).. Plasma homocysteine over 15 micromol/l was a significant risk factor for the presence and extent of coronary artery disease. The mean plasma folate of the population was low and correlated negatively with homocysteine. Although TT genotype was not an independent predictor of coronary artery disease, it was an important predictor of the extent of coronary atherosclerosis and plasma homocysteine, especially in the presence of plasma folate values below the median of the population. These findings may have important implications for folate replacement in patients with the TT genotype.

Topics: Case-Control Studies; Cholesterol; Coronary Disease; Folic Acid; Genotype; Homocysteine; Humans; Lipoproteins, HDL; Methylenetetrahydrofolate Dehydrogenase (NADP); Odds Ratio; Polymerase Chain Reaction; Regression Analysis; Risk; Turkey; Vitamin B 12

Elevated homocyst(e)ine levels are associated with an increased risk of vascular disease, particularly aorto-iliac, coronary and cerebrovascular disease. In patients with confirmed disease, plasma homocyst(e)ine is a strong predictor of death. In addition to B vitamins, folic acid and certain genotypes, renal function is an independent determinant of plasma homocyst(e)ine level. There also may be a polygenic component contributing to elevated homocyst(e)ine levels in confirmed vascular disease. Possible mechanisms of homocyst(e)ine-induced vascular change include proliferation of vascular smooth muscle cells, endothelial cell dysfunction and a procoagulant state. The definition of hyperhomocyst(e)inemia is based on arbitrary cut-points (eg, the 90th percentile). In most populations, this is approximately 15 microM/L. Patients with hyperhomocyst(e)inemia should be treated with at least 400 micrograms of folic acid per day. Alternative treatments are vitamin B6 and B12 supplementation, although optimal doses have yet to be identified.

Topics: Animals; Cardiovascular Diseases; Cerebrovascular Disorders; Coronary Disease; Cricetinae; Female; Folic Acid; Humans; Hyperhomocysteinemia; Male; Middle Aged; Pyridoxine; Risk Factors; Vitamin B 12

Premenopausal black women have a greater rate of coronary artery disease (CAD) than do premenopausal white women. Plasma total homocysteine concentrations, a risk factor for CAD, have not been reported in premenopausal black women.. The purpose of this study was to compare plasma total homocysteine, folate, and vitamin B-12 concentrations in premenopausal black and white women.. Eighty-nine black and 90 white, healthy, premenopausal women living in Portland, OR, were recruited. Dietary histories were obtained by using the Diet Habit Survey, a 40-item eating-behavior questionnaire. Plasma concentrations of total homocysteine, folate, and vitamin B-12 were measured.. Black women had higher plasma total homocysteine (8.32 compared with 7.60 micromol/L;P = 0. 013), lower plasma folate (6.62 compared with 9.88 nmol/L;P < 0. 0001), and higher vitamin B-12 (355 compared with 283 pmol/L;P < 0. 001) concentrations than white women. White women had a greater rate of daily multivitamin supplement use (42.4% compared with 24.7%;P = 0.019) and ate more ready-to-eat cereal than did black women. After adjustment for multivitamin use and intake of ready-to-eat cereal, plasma total homocysteine concentrations did not differ significantly, but plasma folate remained significantly lower in the black women. None of the black women but 12.3% of the white women (P = 0.013) were homozygous for the cytosine to thymidine mutation at nucleotide 677 in the methylenetetrahydrofolate reductase gene.. Black women had higher plasma total homocysteine and lower plasma folate concentrations than white women, largely because of lifestyle factors, which may contribute to the greater rate of CAD in premenopausal black than in white women.

Topics: Adolescent; Adult; Black People; Coronary Disease; Feeding Behavior; Female; Folic Acid; Homocysteine; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Premenopause; Reference Values; Surveys and Questionnaires; Vitamin B 12; White People

Cereal grain flour products fortified with 140 microg folic acid per 100 g flour became widely available in southeast New England by July 1997. We hypothesized that improved folate status secondary to this fortification policy would have a much more limited impact on the prevalence of mild fasting hyperhomocysteinemia in renal transplant versus coronary artery disease patients. Between October 1997 and October 1998, fasting plasma total homocysteine (tHcy), folate and vitamin B12 levels were determined in a total of 86 renal transplant patients with stable allograft function, and 175 coronary artery disease patients whose serum creatinine was (1.4 mg/dl). All subjects lived in the Providence, RI, metropolitan area, and were either non-users of any supplements containing folic acid, vitamins B6 or B12, or had refrained from using such supplements for > or = 6 weeks. Geometric mean fasting tHcy levels were 88.0% higher (15.6 vs. 8.3 micromol/l; P < 0.001), and the prevalence of fasting tHcy levels > or = 12 microM (69.8% vs. 10.9%, P < 0.001) was markedly increased in the renal transplant patients, despite a much younger mean age and a relative preponderance of women. In the era of folic acid fortified flour, hyperhomocysteinemia is much more common in stable renal transplant versus coronary artery disease patients. As a result, renal transplant patients are a preferable high risk target population for controlled trials evaluating the tenable hypothesis that lowering total homocysteine levels will reduce cardiovascular disease outcomes.

Topics: Coronary Disease; Fasting; Female; Flour; Folic Acid; Food, Fortified; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Transplantation; Male; Middle Aged; Vitamin B 12

To examine the relationship between coronary heart disease (CHD) and serum lipid, plasma homocysteine (HCY) as well as the factors related to HCY metabolisms.. The mutation of the 677C-->T transition of 5, 10-methylenetetrahydrofolate reductase (MTHFR) was determined by PCR-based assay. Whole-blood and plasma folate and plasma vitamin B12, as cofactors of MTHFR, were determined by radio-immunologic assay. Plasma HCY was determined by HPLC.. Patients with CHD had elevated plasma HCY concentrations (17.38 +/- 1.94 mumol/L vs 10.25 +/- 1.57 mumol/L, P < 0.01). In patients with myocardial infarction (MI) and family history (FH) of CHD, plasma HCY were elevated even higher (P < 0.05). Plasma HCY concentrations had significant non-linear inverse correlation with plasma folate and B12 concentrations, i.e. the lower the serum folate or B12 concentrations, the higher the plasma HCY concentrations (P < 0.01). Patients with homozygous mutants had higher plasma HCY concentrations. Patients with CHD had increased serum Chol and LDL-C and Apo-B levels (P < 0.01, P < 0.05 and P < 0.05 respectively). But plasma HCY concentrations had no correlation with serum lipid levels. 24.1% of the patients had high lipid and high HCY level, 25.9% had high lipid level and normal HCY level, 20.4% had normal lipid and high HCY level, and 29.6% had normal lipid and HCY level.. HCY may have strong association with the genesis of CHD. Low plasma folate and B12 concentrations may induce Hyperhomocysteinemia [HH(e)]. Plasma HCY concentrations have no correlation with serum lipid levels, so HCY may be an independent risk factor. CHD may be induced by different mechanisms and can be classified into hyperlipidemia, HH (e) and normolipidemia, and normohomocysteinemia.

Topics: 5,10-Methylenetetrahydrofolate Reductase (FADH2); Adult; Aged; Coronary Disease; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Hyperlipidemias; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases; Point Mutation; 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

Topics: Coronary Disease; Dietary Supplements; Female; Folic Acid; Humans; Pyridoxine; Risk Factors; Vitamin B 12

We examined the risk of coronary heart disease associated with homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase gene.. The mutation increases plasma homocysteine levels by impairing its remethylation. Increased plasma homocysteine is an independent risk factor for cardiovascular disease.. This was a case-control study nested within the Health Professionals Follow-up Study. In 1986, 44,940 U.S. male health professionals, aged 40 to 75 years and free from diagnosed cardiovascular disease, provided detailed information on usual dietary intake, including intake of folate, vitamins B2, B6 and B12, and methionine. Between 1993 and 1995, blood samples were provided by approximately 40% of the participants. We compared data from 500 men with nonfatal coronary heart disease, diagnosed between 1986 and 1992, with data from 500 age-matched control subjects who were free of diagnosed cardiovascular disease at the time of the matched case subject's diagnosis.. Frequencies of homozygosity (+/+) and heterozygosity (+/-) for the mutation were 12.2% and 41.8% in case subjects and 14.4% and 40.0% in control subjects. With subjects homozygous (-/-) or heterozygous (+/-) for the wildtype allele as a reference and matched by age, the odds ratio of coronary heart disease was 0.83 (95% confidence interval, 0.57 to 1.19) for +/+ subjects. The odds ratio was unchanged after adjustment for smoking and other risk factors for coronary heart disease. Odds ratios were also calculated within strata for intake of vitamins involved in homocysteine metabolism or methionine, the metabolic precursor of homocysteine. The +/+ genotype was not directly associated with risk of coronary heart disease among men with low (that is, within the lowest quartile) intake (<301 microg/d) of folate, the substrate for methylenetetrahydrofolate reductase; low intake (<1.8 mg/d) of vitamin B2, the cofactor for methylenetetrahydrofolate reductase; low intake (<8.0 microg/d) of vitamin B12, the cofactor for remethylation; low intake (<2.1 mg/d) of vitamin B6, the cofactor in the catabolic pathway of homocysteine; or high intake (>2.4 g/d) of methionine.. In this generally well-nourished population, men with the +/+ genotype for the C677T mutation in the methylenetetrahydrofolate reductase gene have no increase in risk of coronary heart disease, even when intake of folate or other B vitamins is low.

Topics: Adult; Aged; Alleles; Case-Control Studies; Confidence Intervals; Coronary Disease; Diet; Folic Acid; Follow-Up Studies; Genotype; Heterozygote; Homocysteine; Homozygote; Humans; Male; Methionine; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Odds Ratio; Oxidoreductases Acting on CH-NH Group Donors; Pyridoxine; Riboflavin; Risk Factors; Smoking; United States; Vitamin B 12

Hyperhomocysteinemia is now regarded as an established risk factor for coronary artery disease and is present frequently in the general population. However, the diagnostic value of this risk factor relative to others has only occasionally been investigated. We compared the diagnostic value of classic risk factors and of homocysteine in a retrospective case-control study in 191 cases with angiographically established coronary artery disease and 231 healthy controls. Life style habits were assessed by a detailed questionnaire. Laboratory parameters including lipoproteins and blood lipids, homocysteine, folate, and vitamin B12 were measured and their diagnostic value compared with each other by use of receiver-operator characteristic analysis. Comparison of the receiver-operator characteristic curves revealed that homocysteine significantly discriminated between cases and control subjects. High-density-lipoprotein cholesterol, triglycerides and non-esterified fatty acids also had an area under the curve significantly different from 0.5 (the area under the curve representing no discrimination). Homocysteine was weakly related to folate, vitamin B12, age and serum creatinine concentration. We conclude that hyperhomocysteinemia is at least as important as conventional risk factors for coronary artery disease and that receiver operator characteristic analysis of homocysteine is suitable to determine patients at the highest risk for coronary artery disease. Clinical trials testing the effect of homocysteine lowering by vitamin supplementation in the prevention of coronary artery disease are needed.

Topics: Coronary Disease; Demography; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Life Style; Lipids; Lipoproteins; Male; Middle Aged; Odds Ratio; Retrospective Studies; Risk Factors; ROC Curve; Surveys and Questionnaires; Vitamin B 12

Topics: Adult; Coronary Disease; Edible Grain; Folic Acid; Food, Fortified; Humans; Male; Middle Aged; Risk Factors; Vitamin B 12

The data demonstrate that high plasma homocysteine levels and low plasma folate and vitamin B12 levels are associated with a higher prevalence of coronary artery disease (CAD) in older men and women. Elevated plasma homocysteine levels were observed in 43% of the older men with CAD versus 18% of the older men without CAD, and in 37% of the older women with CAD versus 12% of the older women without CAD.

Topics: Age Factors; Aged; Aged, 80 and over; Coronary Disease; Cross-Sectional Studies; Female; Folic Acid; Homocysteine; Humans; Logistic Models; Male; Prevalence; Sex Factors; 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

L-Methionine (0.1 g/kg body wt) was administered to young white [n = 18; mean (+/- SD) age 20.0 +/- 1.0 y] and black [n = 12; mean (+/- SD) age 22.0 +/- 1.3 y] volunteers who had a similar lifestyle and who did not differ significantly from each other with respect to plasma folate or vitamin B-12 concentrations. Blacks, however, had significantly lower plasma pyridoxal-5'-phosphate concentrations compared with whites (P < 0.001). Fasting plasma homocysteine concentrations in blacks and whites were not significantly different. The mean (+/- SD) maximum increase in plasma homocysteine concentration measured after methionine loading was significantly lower (P < 0.01) in blacks (11.0 +/- 3.6 mumol/L) than in whites (18.0 +/- 6.2 mumol/L). Six weeks of vitamin supplementation (1.0 mg folic acid, 400 micrograms vitamin B-12, and 10 mg pyridoxine/d) reduced the mean (+/- SD) fasting plasma homocysteine concentration from 9.6 +/- 3.5 to 7.2 +/- 1.6 mumol/L in whites (P < 0.05) and from 8.4 +/- 2.4 to 5.6 +/- 1.4 mumol/L in blacks (P < 0.01). The mean (+/- SD) maximum increase in plasma homocysteine concentration after methionine loading declined from 18.0 +/- 6.2 to 11.1 +/- 2.3 mumol/L (P < 0.01) in whites, but vitamin supplementation did not have a significant effect on the methionine-load test in black volunteers. A significant race-by-time interaction shows that blacks metabolized homocysteine more effectively than did whites, which may partly explain their relative resistance against coronary heart disease despite a high prevalence of obesity, hypertension, and smoking.

Topics: Adult; Black People; Coronary Disease; Folic Acid; Homocysteine; Humans; Male; Methionine; South Africa; Vitamin B 12; Vitamins; White People

To examine the graded risks for coronary artery disease (CAD) associated with plasma homocyst(e)ine [H(e)] and to evaluate the extent to which this risk is mediated by altered vitamin status, we measured plasma concentrations of H(e), vitamins B6 and B12, and folate as well as other coronary risk factors in subjects with early familial CAD and in control subjects. We studied 120 male and 42 female patients with early CAD who were unrelated to each other but were from families in which at least one other sibling had early CAD. Control subjects were 85 men and 70 women with the same age range (38 to 68) as the subjects with CAD at screening. Increasing H(e) was associated with graded increased risks of CAD that appeared consistent with a multiplicative model. Relative odds for CAD were approximately 12.8 in women when those with H(e) levels of 9 mumol/L and above were compared with those with H(e) levels of 9 mumol/L or less (P = .007). For men, the same comparison yielded relative odds of 13.8 (P = .0002). Plasma H(e) remained a strong, independent risk factor after adjustment for standard risk factors and plasma vitamin levels in multiple logistic regression (relative odds, 8.1 for a 10-mumol/L increase in H(e); 95% confidence interval, 3.2 to 20.4; P < .0001). In multivariate ANCOVA the slope of H(e) versus folate was much steeper in subjects with CAD than in control subjects (P = .0035). These data suggest that high plasma H(e) is an important, independent contributor to risk for early familial CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Coronary Disease; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Male; Middle Aged; Pyridoxine; Regression Analysis; Risk Factors; Vitamin B 12

We determined plasma levels of homocysteine in 584 healthy subjects (380 men and 204 women) from a major utility company in the province of Québec, Canada, and in 150 subjects (123 men and 27 women) with angiographically documented coronary artery disease (CAD) (age < 60 years). Plasma levels of vitamins B12, B6, pyridoxal phosphate (a vitamin B6 derivative), and folate were also determined. Mean homocysteine levels were higher (p < 0.05) in the bottom quartiles for folate, vitamin B12, and pyridoxal phosphate. A significant correlation was noted between homocysteine levels and folate and vitamin B12 levels. No significant correlation was found between plasma homocysteine levels and age, lipids and lipoprotein cholesterol, glucose, and the presence of hypertension or cigarette smoking in healthy subjects or in patients with CAD. Control men had higher homocysteine levels than control women (p < 0.005). Men and women with CAD had higher levels of homocysteine than controls (11.7 +/- 5.8 vs 9.7 +/- 4.9 nmol/ml [p < 0.001] and 12.0 +/- 6.3 vs 7.6 +/- 4.1 nmol/ml, p < 0.01, respectively). Women and men with CAD had similar homocysteine levels. The proportion of patients with CAD having homocysteine levels > 90th percentile of controls was 18.1% for men and 44.4% for women (both p < 0.01). Significantly lower pyridoxal phosphate levels were seen in subjects with CAD, men and women combined (27.7 +/- 29.5 vs 42.1 +/- 38.4 ng/ml, p < 0.005). No significant differences were observed for B12, folate, or total B6.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Chi-Square Distribution; Coronary Disease; Discriminant Analysis; Female; Folic Acid; France; Homocysteine; Humans; Male; Middle Aged; Multivariate Analysis; Pyridoxal Phosphate; Pyridoxine; Quebec; Regression Analysis; Risk Factors; Sex Factors; Vitamin B 12; Vitamin B Complex

High plasma homocyst(e)ine (Hcy) concentrations may be a determinant of coronary artery disease (CAD). Folate and vitamin B-12 are required for the primary metabolic pathway to reduce Hcy concentrations. The interrelationships of Hcy and these two vitamin cofactors were investigated in a case-control study of 101 white males aged 30-50 y with angiographically demonstrated CAD, and 108 white male, similarly aged, control subjects living in the same community as the patients. The odds ratio (OR) of CAD per quartile increase of plasma Hcy concentration based on control values was 1.6 (95% CI: 1.3, 2.1). After age, HDL and LDL cholesterol, body mass index, smoking, hypertension, and diabetes were controlled for, Hcy remained an independent risk factor (OR: 1.4; 95% CI: 1.0, 2.0). The OR change per quartile increase of folate concentration was 0.8 (95% CI: 0.6, 1.0). This difference was reduced (OR: 0.9; 95% CI: 0.7, 1.2) after Hcy adjustment. No difference in the geometric mean of vitamin B-12 concentration was found between patients and control subjects, both 5.8 nmol/L. However, after Hcy and the other CAD risk factors were controlled for, the OR per quartile increase in vitamin B-12 concentration was 1.5 (95% CI: 1.0, 1.8). Reduction in plasma Hcy by interventions to increase plasma folate concentration may decrease CAD risk.

Topics: Adult; Case-Control Studies; Coronary Disease; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Risk Factors; Vitamin B 12

Topics: Amino Acids; Anticoagulants; Choline; Coronary Disease; Folic Acid; Homocysteine; Humans; Hydroxyethylrutoside; Pyridoxine; Riboflavin; Vitamin B 12

Elevated plasma homocysteine and lipid levels are risk factors for atherosclerosis. The plasma levels of homocysteine, determined in acid hydrolyzates of plasma, were found to be correlated with total cholesterol (r = 0.47, P less than 0.001), triglycerides (r = 0.40, P less than 0.01), and body mass index (r = 0.42, P less than 0.01) in 52 males, aged 30-60. A group of 12 male survivors of acute myocardial infarction was given pyridoxine, folate, cobalamin, choline, riboflavin, and troxerutin for 21 days. The plasma concentrations of homocysteine and alpha-amino adipic acid declined to 68% (P less than 0.001) and 57% (P less than 0.001) of the pretreatment values, and the cholesterol, triglycerides, and LDL apo B declined to 79% (P less than 0.001), 68% (P less than 0.01), and 63% (P less than 0.001) of the pretreatment values, respectively. The results suggest a new strategy for control of the metabolic abnormalities in atherosclerosis through the use of naturally occurring, non-toxic nutrients which minimize homocysteine accumulation.

Topics: Adult; Anticoagulants; Choline; Coronary Artery Disease; Coronary Disease; Drug Therapy, Combination; Folic Acid; Homocysteine; Humans; Hydroxyethylrutoside; Lipids; Male; Middle Aged; Pyridoxine; Riboflavin; Vitamin B 12

Topics: Aged; Coronary Disease; Drug Therapy, Combination; Folic Acid; Humans; Middle Aged; Myocardial Contraction; Myocardium; Orotic Acid; Vitamin B 12

Topics: Adult; Anemia, Hypochromic; Child; Cholelithiasis; Coronary Disease; Diabetes Mellitus; Diet Therapy; Diet, Diabetic; Diet, Reducing; Female; Humans; Hypertension; Male; Middle Aged; Obesity; Osteoporosis; Peptic Ulcer; Pregnancy; Ureteral Calculi; Urinary Bladder Calculi; Vitamin B 12; Vitamin B 6 Deficiency

Topics: Anemia, Pernicious; Cholesterol; Coronary Disease; Humans; Lipid Metabolism; Male; Vitamin B 12

Topics: Adult; Aged; Coronary Disease; Female; Folic Acid; Humans; Male; Middle Aged; Orotic Acid; RNA; Stimulation, Chemical; Vitamin B 12

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

Topics: Adenosine Triphosphate; Blood Proteins; Calcium; Chelating Agents; Coronary Disease; Female; Folic Acid; Heart; Hemodynamics; Humans; Male; Middle Aged; Pantothenic Acid; Potassium; Pyruvates; Rheumatic Heart Disease; Strophanthins; Sulfhydryl Compounds; Vitamin B 12

Topics: Ascorbic Acid; Coronary Disease; Humans; Pyridoxine; Vitamin B 12; Vitamins

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: Aged; Arteriosclerosis Obliterans; Choline; Coronary Disease; Folic Acid; Gangrene; Heparin; Humans; Male; Middle Aged; Niacinamide; Sympathectomy; Thrombosis; Vascular Diseases; Vasodilator Agents; Vitamin B 12

Topics: Adolescent; Adult; Aged; Bilirubin; Blood Proteins; Body Weight; Central Nervous System; Cholesterol; Coronary Disease; Diet, Vegetarian; Dietary Proteins; Female; Folic Acid; Humans; Male; Middle Aged; Nutritional Physiological Phenomena; Sex Factors; Smoking; Time Factors; Urea; Vitamin B 12

Topics: Adult; Angina Pectoris; Blood Cell Count; Blood Platelets; Coronary Disease; Heparin; Humans; Middle Aged; Myocardial Infarction; Nialamide; Platelet Adhesiveness; Vitamin B 12

Topics: Adult; Blood Protein Electrophoresis; Carbon Isotopes; Coronary Disease; Diarrhea; Female; Humans; Hypercholesterolemia; Ileum; Lipids; Male; Middle Aged; Time Factors; Vitamin A; Vitamin B 12; Xylose

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: Adolescent; Adult; Aged; Anemia; Child; Cholesterol; Chronic Disease; Coronary Disease; Female; Humans; Lipids; Male; Middle Aged; Phospholipids; Splenectomy; Triglycerides; Vitamin B 12

Topics: Adolescent; Adult; Aged; Blood; Cerebrovascular Disorders; Cobalt Isotopes; Coronary Disease; Female; Glomerular Filtration Rate; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Pre-Eclampsia; Pregnancy; Statistics as Topic; Uric Acid; Vitamin B 12

Topics: Adenine Nucleotides; Adult; Aged; Coronary Disease; Female; Heart Diseases; Humans; Hypertension; Male; Middle Aged; Myocarditis; Thiamine Pyrophosphate; Vitamin B 12

Topics: Cardiotonic Agents; Coronary Artery Disease; Coronary Disease; Hematinics; Humans; Testosterone; Vitamin B 12; Vitamin B Complex

Topics: Coronary Disease; Corrinoids; Folic Acid; Hematinics; Syndrome; Vitamin B 12

Topics: Coronary Artery Disease; Coronary Disease; Corrinoids; Folic Acid; Hematinics; Humans; Vitamin B 12; Vitamin B Complex