vitamin-b-12 and Myocardial-Ischemia

In the Norwegian Vitamin Trial and the Western Norway B Vitamin Intervention Trial, patients were randomly assigned to homocysteine-lowering B-vitamins or no such treatment. We investigated their effects on cardiovascular outcomes in the trial populations combined, during the trials and during an extended follow-up, and performed exploratory analyses to determine the usefulness of homocysteine as a predictor of cardiovascular outcomes.. Pooling of data from two randomized controlled trials (1998-2005) with extended post-trial observational follow-up until 1 January 2008.. Thirty-six hospitals in Norway.. 6837 patients with ischaemic heart disease.. One capsule per day containing folic acid (0.8 mg) plus vitamin B12 (0.4 mg) and vitamin B6 (40 mg), or folic acid plus vitamin B12, or vitamin B6 alone or placebo.. Major adverse cardiovascular events (MACEs; cardiovascular death, acute myocardial infarction or stroke) during the trials and cardiovascular mortality during the extended follow-up.. Folic acid plus vitamin B12 treatment lowered homocysteine levels by 25% but did not influence MACE incidence (hazard ratio, 1.07; 95% CI, 0.95-1.21) during 39 months of follow-up, or cardiovascular mortality (hazard ratio, 1.12; 95% CI, 0.95-1.31) during 78 months of follow-up, when compared to no such treatment. Baseline homocysteine level was not independently associated with study outcomes. However, homocysteine concentration measured after 1-2 months of folic acid plus vitamin B12 treatment was a strong predictor of MACEs.. We found no short- or long-term benefit of folic acid plus vitamin B12 on cardiovascular outcomes in patients with ischaemic heart disease. Our data suggest that cardiovascular risk prediction by plasma total homocysteine concentration may be confined to the homocysteine fraction that does not respond to B-vitamins.

Topics: Capsules; Double-Blind Method; Drug Combinations; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Myocardial Ischemia; Patient Compliance; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Treatment Outcome; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Present article is devoted to the study of the correlation between vitamin B12 serum level, hyperhomocysteinaemia and dyslipidemia. During research there were discovered that the lowest vitamin B12 serum level and the highest homocysteine serum level have been registrated in associated pathology (ischemic heart disease and acid peptic disease according to long-term proton pump inhibitor use) patients. It was shown evident correlation between that changes and dyslipidemia. Тhe complex therapy that includes parenteral B12 supplementation leads to more effective correction of hyperhomocysteinaemia and dyslipidemia in patients with comorbidity of ischemic heart disease and acid peptic disease with long-term use of proton pump inhibitors.

Topics: Cholesterol; Comorbidity; Dyslipidemias; Homocysteine; Humans; Hyperhomocysteinemia; Infusions, Parenteral; Lipoproteins, LDL; Myocardial Ischemia; Peptic Ulcer; Proton Pump Inhibitors; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

The lowest dose of folic acid required to achieve effective reductions in homocysteine is controversial but important for food fortification policy given recent concerns about the potential adverse effects of overexposure to this vitamin.. We compared the effectiveness of 0.2 mg folic acid/d with that of 0.4 and 0.8 mg/d at lowering homocysteine concentrations over a 6-mo period.. A randomized dose-finding trial with folic acid was conducted. Of 203 participants screened, 101 patients with ischemic heart disease and 71 healthy volunteers completed the study. Participants were randomly assigned to receive placebo or folic acid at doses of 0.2, 0.4, or 0.8 mg/d for 26 wk; subsamples of patients with ischemic heart disease were also examined at 6 or 12 wk.. Participants with higher baseline homocysteine concentrations had the greatest reductions in homocysteine in response to folic acid doses of 0.2 mg (-20.6%), 0.4 mg (-20.7%), and 0.8 mg (-27.8%); in those with lower baseline homocysteine concentrations, the responses were -8.2%, -8.9%, and -8.3%, respectively. No significant differences in homocysteine responses to the different doses were observed. In the patient group sampled at intervals during the intervention, the maximal homocysteine response appeared to be achieved by 6 wk in the 0.8-mg/d group and by 12 wk in the 0.4-mg/d group. However, the homocysteine response was suboptimal in the 0.2-mg/d group at both 6 and 12 wk compared with that at 26 wk.. A folic acid dose as low as 0.2 mg/d can, if administered for 6 mo, effectively lower homocysteine concentrations. Higher doses may not be necessary because they result in no further significant lowering, whereas doses even lower than 0.2 mg/d may be effective in the longer term. Previous trials probably overestimated the folic acid dose required because of a treatment duration that was too short. This trial was registered at clinicaltrials.gov as ISRCTN45296887.

Topics: Aged; Dose-Response Relationship, Drug; Female; Folic Acid; Food, Fortified; Homocysteine; Humans; Male; Middle Aged; Myocardial Ischemia; Neural Tube Defects; Nutrition Policy; Vitamin B 12

No data are currently available on the prevalence and control of cardiovascular (CV) risk factors in secondary prevention depending on the cardiac or cerebral localization of the ischemic disease. We investigated the prevalence and control of modifiable CV risk factors, as well as the determinants of CV risk factors' control and adequate treatment in a secondary prevention cohort, the SU-FOL-OM3 study cohort, to determine the role of the localization of the ischemic disease including events.. A total of 2491 patients were included in the study. The prevalence of all modifiable risk factors was high in both coronary heart disease and cerebrovascular disease (CVD) groups. Control of all risk factors and the presence of antiplatelet medication were noted in 29.6% of patients with coronary heart disease and 11% of patients with CVD. The cardiac localization of the including event was independently associated with the control of each of the risk factors studied (hypertension, low-density lipoprotein-cholesterol, smoking) and to the control of all risk factors present and prescription of antiplatelet therapy with an odds ratio (95% confidence interval) of 2.72 (1.97-3.75).. There is a need to improve the control of CV risk factors in secondary prevention patients. This is particularly crucial for patients with CVD.

Topics: Aged; Anticholesteremic Agents; Antihypertensive Agents; Biomarkers; Brain Ischemia; Chi-Square Distribution; Cholesterol, LDL; Cohort Studies; Diabetes Mellitus; Dietary Supplements; Double-Blind Method; Fatty Acids, Omega-3; Female; Folic Acid; France; Humans; Hypercholesterolemia; Hypertension; Hypoglycemic Agents; Logistic Models; Male; Middle Aged; Myocardial Ischemia; Odds Ratio; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Secondary Prevention; Smoking Cessation; Treatment Outcome; Vitamin B 12; Vitamin B 6

Elevated plasma total homocysteine appears to be related to endothelial dysfunction and impaired nitric oxide production. We aimed to investigate [1] whether elevated levels of plasma total homocysteine are associated with high plasma levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, and [2] whether reduction of plasma total homocysteine levels by folate and vitamin B supplementation lowers plasma concentration of asymmetric dimethylarginine.. Sixty patients with ischaemic heart disease and with plasma total homocysteine levels of 15.0 micromol L-1 were randomized to open therapy with folic acid, pyridoxine and cyancobalamin for 3 months (n = 30) or to no treatment (n = 30). Samples were also obtained from 34 patients with plasma total homocysteine levels of 8.0 micromol L-1 on admission.. Plasma asymmetric dimethylarginine concentrations in patients with elevated total homocysteine levels were not significantly higher (0.68 +/- 0.19 micromol L-1) than in patients with low total homocysteine levels (0.61 +/- 0.10 micromol L-1; P = 0.08). Plasma asymmetric dimethylarginine level in the vitamin supplemented group was 0.65 +/- 0.12 micromol L-1 before, and 0.64 +/- 0.12 micromol L-1 after 3 months of vitamin supplementation (NS). Plasma asymmetric dimethylarginine levels were correlated with serum cystatin C levels (P < 0.001).. A nonsignificant trend to increased plasma levels of asymmetric dimethylarginine in patients with high plasma total homocysteine levels may be explained by concomitant subtle renal dysfunction. Substantial reduction of plasma total homocysteine did not affect the level of plasma asymmetric dimethylarginine.

Topics: Adult; Arginine; Female; Folic Acid; Humans; Hyperhomocysteinemia; Male; Middle Aged; Myocardial Ischemia; Nitric Oxide Synthase; Pyridoxine; Vitamin B 12

Recently, concern has been raised about the safety of folic acid, particularly in relation to cancer risk.. To evaluate effects of treatment with B vitamins on cancer outcomes and all-cause mortality in 2 randomized controlled trials.. Combined analysis and extended follow-up of participants from 2 randomized, double-blind, placebo-controlled clinical trials (Norwegian Vitamin Trial and Western Norway B Vitamin Intervention Trial). A total of 6837 patients with ischemic heart disease were treated with B vitamins or placebo between 1998 and 2005, and were followed up through December 31, 2007.. Oral treatment with folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) and vitamin B(6) (40 mg/d) (n = 1708); folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) (n = 1703); vitamin B(6) alone (40 mg/d) (n = 1705); or placebo (n = 1721).. Cancer incidence, cancer mortality, and all-cause mortality.. During study treatment, median serum folate concentration increased more than 6-fold among participants given folic acid. After a median 39 months of treatment and an additional 38 months of posttrial observational follow-up, 341 participants (10.0%) who received folic acid plus vitamin B(12) vs 288 participants (8.4%) who did not receive such treatment were diagnosed with cancer (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.41; P = .02). A total of 136 (4.0%) who received folic acid plus vitamin B(12) vs 100 (2.9%) who did not receive such treatment died from cancer (HR, 1.38; 95% CI, 1.07-1.79; P = .01). A total of 548 patients (16.1%) who received folic acid plus vitamin B(12) vs 473 (13.8%) who did not receive such treatment died from any cause (HR, 1.18; 95% CI, 1.04-1.33; P = .01). Results were mainly driven by increased lung cancer incidence in participants who received folic acid plus vitamin B(12). Vitamin B(6) treatment was not associated with any significant effects.. Treatment with folic acid plus vitamin B(12) was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods.. clinicaltrials.gov Identifier: NCT00671346.

Topics: Aged; Dietary Supplements; Female; Folic Acid; Follow-Up Studies; Humans; Male; Middle Aged; Mortality; Myocardial Ischemia; Neoplasms; Norway; Proportional Hazards Models; Randomized Controlled Trials as Topic; Vitamin B 12; Vitamin B 6; Vitamin B Complex

The extent of genetic influence on plasma homocysteine, a risk factor for ischaemic heart disease, is uncertain. Many association studies have investigated common polymorphisms and their role in hyperhomocysteinaemia, but only the thermolabile variant of methylene tetrahydrofolate reductase (MTHFR) has shown an association (small but robust).. To estimate the heritability of plasma homocysteine and the contributions of well-studied common SNPs in the three main candidate genes in the homocysteine methylation pathway.. Twin study.. We studied 216 monozygotic and 790 dizygotic pairs of twins; all were women. Blood was collected after overnight fasting for measurement of homocysteine, folate, vitamin B12, and extraction of DNA. Heritability was estimated by structural modelling, including correction for known environmental influences, particularly serum folate. The frequency of a common coding SNP in MTHFR and methionine synthase (MTR), and two coding SNPs in methionine synthase reductase (MTRR) were measured in dizygotic twins by ABI 7700 Sequence Detection, and the contribution of each to homocysteine variance was determined.. The heritability of homocysteine was 57% (95%CI 51-63%). The highest contribution to homocysteine was serum folate, accounting for 10.13% of variance. This was twice the total genetic contribution of 4.56%, and only the C1763T SNP of MTRR showed significant association with homocysteine.. Homocysteine has one of the highest heritabilities of common risk factors for ischaemic heart disease. This is not accounted for by the commonly studied SNPs in MTHFR, MTR and MTRR.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Adolescent; Adult; Aged; Diseases in Twins; Female; Folic Acid; Homocysteine; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Myocardial Ischemia; Polymorphism, Single Nucleotide; Surveys and Questionnaires; Vitamin B 12

Homocysteine (Hcy) is recognised as a risk factor for IHD. Serum Hcy is negatively correlated with serum folate levels, the main sources of which are fruits, vegetables and legumes. The present case-control study was designed to examine the relationship between serum Hcy levels and IHD and to assess the role of dietary factors in the southern Mediterranean population of Crete, Greece. Serum Hcy, folate, vitamin B12, creatinine and glucose levels and a full lipid profile were measured in 152 patients with established IHD, median age 64 (range 33-77) years, and 152 healthy control subjects, age- and sex-matched. Dietary data were assessed using a 3 d food intake record. Compared with controls, patients with IHD had significantly higher daily intakes of vitamin B12 and MUFA and significantly lower intakes of carbohydrate, fibre, folate, cholesterol, n-3 fatty acids and total trans unsaturated fatty acids. Moreover, patients had significantly higher serum Hcy, vitamin B12 and creatinine levels, but significantly lower folate. Serum folate concentrations in both groups had a significant positive correlation with dietary fibre consumption and a significant inverse correlation with vitamin B12 intake. IHD patients should be encouraged to increase their daily dietary intake of fibre, folate and n-3 fatty acids, which are significant components of the traditional Cretan Mediterranean diet. Where dietary folate intake is inadequate, folate supplements are recommended to reduce elevated Hcy levels.

Topics: Adult; Aged; Case-Control Studies; Cholesterol; Creatinine; Diet; Female; Folic Acid; Greece; Homocysteine; Humans; Male; Middle Aged; Myocardial Ischemia; Vitamin B 12

In the latest years it became clear that beside traditional cardiovascular risk factors the high plasma homocysteine level increases the risk of atherosclerotic diseases too. Metaanalysis of 27 papers found that 10% of population's coronary risk is attributable to homocysteine and a 5 mumol/l increase in its plasma level elevates the coronary risk by as much as 0.5 mumol/l cholesterol increase. Recent studies have shown an inverse relation between the levels of plasma homocysteine and that of folic acid, vitamin B6, vitamin B12. The latters are cofactors and substrates of the homocysteine and methionin metabolism. The plasma total cholesterol, HDL-cholesterol, triglyceride, lipoprotein(a), Apo A1, Apo B and homocysteine concentrations were examined in 39 patients suffering from coronary artery disease treated in the Cardiac Rehabilitation Department of our hospital. Twenty of them were treated by folic acid and vitamin B6 for a three week period. The mean (+/- SD) plasma homocysteine concentration was 15.60 +/- 6.14 mumol/l. In the treated subgroup the mean (+/- SD) plasma homocysteine concentration was 17.3 +/- 7.00 mumol/l, the mean (+/- SD) plasma folic acid level was 8.58 +/- 4.6 mumol/l. After the three week treatment period (folic acid and vitamin B6) the plasma homocysteine level decreased by 26.5% (p = 0.012), that of folic acid increased by 68.7% (p = 0.002). From the plasma lipids the level of total- and LDL-cholesterol decreased significantly (6.7% and 10.4%, P < 0.05), caused by the strict diet during hospital treatment. As for the genetic polymorphism of the V677 gen of the metylenetetrahydrofolate-reductase (MTHFR) enzyme there was a significant correlation with homocysteine level (r = 0.436, p = 0.010), and a negative, but not significant correlation with the folic acid level (r = -0.354).

Topics: Aged; Drug Administration Schedule; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Lipids; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Myocardial Ischemia; Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Risk Factors; Vitamin B 12; Vitamin B 6