vitamin-b-12 and Coronary-Artery-Disease

Nutritional factors such as magnesium, folic acid, vitamins B12 and B6, L-arginine, and polyunsaturated fatty acids (PUFAs) appear to be significantly beneficial for patients with coronary artery disease (CAD), and in the prevention and arresting the progression of HF and cardiac arrhythmias. Additionally, ingestion of adequate amounts of protein and maintaining normal concentrations of plasma albumin seem to be essential for these patients. These nutrients closely interact with the metabolism of L-arginine-nitric oxide (NO) system, essential fatty acids, and eicosanoids such that beneficial products such as NO, prostaglandin E1, prostacyclin, prostaglandin I3, lipoxins, resolvins, and protectins are generated and synthesis of proinflammatory cytokines is suppressed that results in platelet anti-aggregation, vasodilation, angiogenesis, and prevention of CAD, cardiac arrhythmias, and stabilization of HF. This implies that individuals at high risk for CAD, cardiac arrhythmias, and HF and those who have these diseases need to be screened for plasma levels of magnesium, folic acid, vitamins B12 and B6, L-arginine, NO, various PUFAs, lipoxin A4, resolvins, protectins, asymmetrical dimethylarginine (an endogenous inhibitor of NO), albumin, and various eicosanoids and cytokines and correct their abnormalities to restore normal physiology.

Topics: Alprostadil; Anti-Inflammatory Agents; Arginine; CD59 Antigens; Coronary Artery Disease; Diabetes Mellitus, Type 2; Epoprostenol; Fatty Acids, Essential; Fatty Acids, Unsaturated; Female; Folic Acid; Heart Failure; Humans; Hypertension; Lipoxins; Magnesium; Male; Middle Aged; Nitric Oxide; Nutritional Status; Serum Albumin; Vasodilation; Vitamin B 12; Vitamin B 6

Laboratory and observational studies suggest that antioxidant and B vitamin supplementation may prevent atherosclerosis. Although trials have not shown a benefit of these supplements on clinical cardiovascular events, it is unknown whether they affect the progression of atherosclerosis as measured by imaging techniques.. The objective was to perform a meta-analysis of randomized controlled trials of the effect of vitamin-mineral supplementation on atherosclerosis progression.. We searched the MEDLINE, EMBASE, and CENTRAL databases for relevant studies. No language restrictions were applied. We separately analyzed trials using antioxidants (vitamins E and C, beta-carotene, or selenium) and trials using B vitamins (folate, vitamin B-6, or vitamin B-12). The progression of atherosclerosis was evaluated by B-mode ultrasound, intravascular ultrasound, or angiography. Effect sizes were calculated for the difference in slope of atherosclerosis progression between participants assigned to supplements and those assigned to the control group.. In trials not involving percutaneous transluminal coronary angioplasty, the pooled effect size was -0.06 (95% CI: -0.20, 0.09; 7 trials) for antioxidants and -0.93 (95% CI: -2.11, 0.26; 4 trials) for B vitamins. In trials involving percutaneous transluminal coronary angioplasty, the pooled relative risk of restenosis was 0.82 (95% CI: 0.54, 1.26; 3 trials) for antioxidants and 0.84 (95% CI: 0.34, 2.07; 2 trials) for B vitamins.. Our meta-analysis showed no evidence of a protective effect of antioxidant or B vitamin supplements on the progression of atherosclerosis, thus providing a mechanistic explanation for their lack of effect on clinical cardiovascular events.

Topics: Adult; Aged; Angiography; Angioplasty, Balloon, Coronary; Antioxidants; Ascorbic Acid; Atherosclerosis; beta Carotene; Coronary Artery Disease; Dietary Supplements; Disease Progression; Female; Folic Acid; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Selenium; Trace Elements; Ultrasonography, Interventional; Vitamin B 12; Vitamin B 6; Vitamin E; Vitamins

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

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

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

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

Homocysteine is increasingly recognized as a risk factor for coronary artery disease. An understanding of its metabolism and of the importance of vitamins B6 and B12 and folate as well as enzyme levels in its regulation will aid the development of therapeutic strategies that, by lowering circulating concentrations, may also lower risk. Possible mechanisms by which elevated homocysteine levels lead to the development and progression of vascular disease include effects on platelets, clotting factors and endothelium. This review presents the clinical and basic scientific evidence supporting the risk and mechanisms of vascular disease associated with elevated homocysteine concentrations as well as the results of preliminary therapeutic trials.

Topics: Coronary Artery Disease; Folic Acid; Homocysteine; Homocystinuria; Humans; Pyridoxine; Risk Factors; Vitamin B 12

Fibrin clot structure/function contributes to cardiovascular disease. We examined sulfur-containing metabolites as determinants of fibrin clot lysis time (CLT) and maximum absorbance (Absmax) in relation to outcomes in coronary artery disease (CAD) patients. Effects of B-vitamin/folate therapy on CLT and Absmax were studied. Plasma samples were collected from 1,952 CAD patients randomized in a 2 x 2 factorial design to (i) folic acid, vitamins B12, B6; (ii) folic acid, vitamin B12; (iii) vitamin B6; (iv) placebo for 3.8 years in the Western Norway B-Vitamin Intervention Trial. Clot lysis time (CLT) and maximum absorbance (Absmax) were determined using a validated turbidimetric assay. Acute myocardial infarction (AMI) and mortality were assessed during a 7-year follow-up. Data were analyzed using bivariate and multiple regression. Survival free of events was studied using Kaplan Mayer plots. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. Baseline urinary homocysteine (uHcy)-thiolactone and plasma cysteine (Cys) were significantly associated with CLT while plasma total Hcy was significantly associated with Absmax, independently of fibrinogen, triglycerides, vitamin E, glomerular filtration rate, body mass index, age, sex plasma creatinine, CRP, HDL-C, ApoA1, and previous diseases. B-vitamins/folate did not affect CLT and Absmax. Kaplan-Meier analysis showed associations of increased baseline CLT and Absmax with worse outcomes. In Cox regression analysis, baseline CLT and Absmax (>cutoff) predicted AMI (CLT: HR 1.58, 95% CI 1.10-2.28; P = 0.013. Absmax: HR 3.22, CI 1.19-8.69; P = 0.021) and mortality (CLT: HR 2.54, 95% CI 1.40-4.63; P = 0.002. Absmax: 2.39, 95% CI 1.17-4.92; P = 0.017). After adjustments for other prognostic biomarkers these associations remained significant. Cys and uHcy-thiolactone, but not tHcy, were significant predictors of AMI in Cox regression models that included CLT. Conclusions uHcy-thiolactone and plasma Cys are novel determinants of CLT, an important predictor of adverse CAD outcomes. CLT and Absmax were not affected by B-vitamin/folate therapy, which could account for the lack of efficacy of such therapy in CAD. Trial registration: URL: http://clinicaltrials.gov. Identifier: NCT00354081.

Topics: Coronary Artery Disease; Fibrin; Folic Acid; Homocysteine; Humans; Myocardial Infarction; Prognosis; Risk Factors; Thrombosis; Vitamin B 12; Vitamin B Complex

The health benefits of red furu in young, healthy volunteers had not been adequately investigated. The aim of this study was to determine the effect of a single meal containing red furu on serum vitamin B-12 (B-12), homocysteine and other cardiometabolic risk factors compared with that of tofu.. Twenty-three healthy volunteers from Zhejiang University, China, were randomly assigned to two groups of consumption, either red furu (n=11, 5 women and 6 men) or tofu (n=12, 6 women and 6 men). Volunteers consumed one breakfast meal composed of either 50 g of red furu (intervention group) or 50 g of tofu (non-active comparison group) with two slices of bread. Fasting blood was collected at 0 h, 24 h, and 72 h. Standard methods were used to measure the volunteers' biochemical parameters.. The consumption of 50 g of red furu a day did not significantly affect serum B-12 and showed a non-significant trend to reduce serum homocysteine. In the red furu group, but not in tofu group, serum concentrations of B-12 and folate were negatively associated with homocysteine, and B-12 was positively associated with folate.. A breakfast meal with 50 g of red furu containing 0.096 μg of B-12 did not increase serum B-12 in healthy volunteers. These results suggested that one meal containing B-12 could be sufficient to reduce serum Hcy.

Topics: Adult; Cardiometabolic Risk Factors; Coronary Artery Disease; Female; Healthy Volunteers; Homocysteine; Humans; Male; Phytotherapy; Soy Foods; Vitamin B 12; Young Adult

Increased epicardial adipose tissue (EAT), pericardial adipose tissue (PAT), periaortic adipose tissue (PaAT), and subcutaneous adipose tissue (SAT) are mediators of metabolic risk, and are associated with the severity of coronary artery calcium (CAC). Aged garlic extract (AGE) has been shown to reduce the progression of coronary atherosclerosis. This study evaluates the effect of AGE with supplements (AGE+S) on EAT, PAT, SAT, and PaAT.. Sixty asymptomatic participants participated in a randomized trial evaluating the effect of AGE+S versus placebo on coronary atherosclerosis progression, and underwent CAC at baseline and after 12 months of treatment. EAT, PAT, PaAT, and SAT volumes were measured on CAC scans. PAT was calculated as: intrathoracic adipose tissue-EAT. SAT was defined as the volume of fat depot anterior to the sternum and posterior to the vertebra. PaAT was defined as fat depot around the descending aorta.. At 1 year, the increase in EAT, PAT, PaAT, and SAT was significantly lower in the AGE+S as compared with the placebo group (P<0.05). The odds ratios of increase in EAT, PAT, PaAT, and SAT were 0.63 [95% confidence interval (CI): 0.43-0.90], 0.72 (95% CI: 0.45-0.93), 0.81 (95% CI: 0.65-0.98), and 0.87 (CI: 0.52-0.98), respectively, compared with the placebo group, which even remained significant (all P<0.05) after adjustment for cardiovascular risk factors and statin therapy and BMI.. This study shows that AGE+S is associated with favorable effects on reducing the progression rate of adipose tissue volumes.

Topics: Aged; Arginine; Coronary Artery Disease; Coronary Vessels; Dietary Supplements; Disease Progression; Double-Blind Method; Female; Folic Acid; Garlic; Humans; Male; Middle Aged; Pericardium; Plant Extracts; Subcutaneous Fat; Vascular Calcification; Vitamin B 12; Vitamin B 6; Vitamin B Complex

We previously showed that treatment with folic acid (FA)/B12 was associated with more rapid progression of coronary artery disease (CAD). High doses of FA may induce methylation by increasing the availability of S-adenosyl-methionine (SAM). Asymmetric dimethylarginine (ADMA) and trimethyllysine (TML) are both produced through proteolytic release following post-translational SAM-dependent methylation of precursor amino acid. ADMA has previously been associated with CAD. We investigated if plasma levels of ADMA and TML were associated with progression of CAD as measured by quantitative coronary angiography (QCA).. 183 patients from the Western Norway B Vitamin Intervention Trial (WENBIT) undergoing percutaneous coronary intervention (PCI) were randomized to daily treatment with 0.8 mg FA/0.4 mg B12 with and without 40 mg B6, B6 alone or placebo. Coronary angiograms and plasma samples of ADMA and TML were obtained at both baseline and follow-up (median 10.5 months). The primary end-point was progression of CAD as measured by diameter stenosis (DS) evaluated by linear quantile mixed models.. A total of 309 coronary lesions not treated with PCI were identified. At follow-up median (95% CI) DS increased by 18.35 (5.22-31.49) percentage points per µmol/L ADMA increase (p-value 0.006) and 2.47 (0.37-4.58) percentage points per µmol/L TML increase (p-value 0.021) in multivariate modeling. Treatment with FA/B12 (±B6) was not associated with ADMA or TML levels.. In patients with established CAD, baseline ADMA and TML was associated with angiographic progression of CAD. However, neither ADMA nor TML levels were altered by treatment with FA/B12 (±B6).. Controlled-Trials.com NCT00354081.

Topics: Adenosine; Aged; Arginine; Coronary Angiography; Coronary Artery Disease; Disease Progression; Ethionine; Female; Folic Acid; Follow-Up Studies; Humans; Lysine; Male; Methylation; Middle Aged; Treatment Outcome; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Plasma concentration of total homocysteine is associated with risk of cardiovascular disease in epidemiological studies. We wanted to examine the effects of B-vitamin therapy, which may lower total homocysteine, on coronary flow and vascular function in patients with established coronary artery disease (CAD).. Forty patients with stable CAD, mean (standard deviation) aged 57.8 (9.0) years, recruited into the Western Norway B-Vitamin Intervention Trial, were randomly assigned to daily oral treatment with 0.8 mg of folic acid and 0.4 mg of vitamin B12 or placebo, and 40 mg of vitamin B6 or placebo, using a 2 × 2 factorial design. At baseline, and after 9 and 24 months, coronary blood flow was assessed by coronary angiography and Doppler flow-wire measurements during intracoronary infusion of saline (basal), incremental doses of acetylcholine, adenosine, and nitroglycerin.. We found a significant increase in basal (P < 0.02) and adenosine-induced (P < 0.05) coronary blood flow in patients who received folic acid/vitamin B12 for 24 months, compared with placebo or vitamin B6 alone. Folic acid/vitamin B12 or vitamin B6 treatment did not change endothelial-dependent response after acetylcholine infusion or flow-dependent proximal dilatation in response to adenosine-induced maximal hyperemia (P ≥ 0.45).. Long-term treatment with a combination of folic acid and vitamin B12 increase basal and adenosine-induced maximal coronary blood flow. This may reflect improved microvascular function in patients with stable CAD.

Topics: Acetylcholine; Adenosine; Aged; Coronary Angiography; Coronary Artery Disease; Coronary Circulation; Double-Blind Method; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Laser-Doppler Flowmetry; Male; Middle Aged; Time Factors; Vitamin B 12; Vitamin B 6

Total plasma homocysteine (tHcy) is an independent risk factor for coronary artery disease, and tHcy is lowered by B vitamins. To assess the effect of homocysteine-lowering B-vitamin treatment on angiographic progression of coronary artery disease, this substudy of the Western Norway B Vitamin Intervention Trial (WENBIT) included patients who had undergone percutaneous coronary intervention. The patients were randomized to daily oral treatment with folic acid, vitamin B(12), and vitamin B(6) or placebo in a 2 x 2 factorial design. The coronary angiograms obtained at baseline and follow-up were evaluated. The primary angiographic end points were the changes in minimum lumen diameter and diameter stenosis. A total of 348 subjects (288 men) with a mean +/- SD age of 60 +/- 10.2 years were followed up for a median of 10.5 months (twenty-fifth, seventy-fifth percentile 9.2, 11.8). The baseline median plasma tHcy level was 10.0 mumol/L (twenty-fifth, seventy-fifth percentile 8.1, 11.0), and treatment with folic acid/vitamin B(12) lowered the tHcy levels by 22%. At follow-up, we found 309 lesions with a significant decrease from baseline in the minimum lumen diameter of a mean of -0.16 +/- 0.4 mm and an increase in the diameter stenosis of 4.4 +/- 0.7%. Treatment with folic acid/vitamin B(12) or vitamin B(6) was not associated with a change in diameter stenosis or minimum lumen diameter. In a post hoc analysis, folic acid/vitamin B(12) treatment was significantly associated with rapid progression (odds ratio 1.84, 95% confidence interval 1.07 to 3.18). In conclusion, vitamin B treatment showed no beneficial effect on the angiographic progression of coronary artery disease, and the post hoc analyses suggested that folic acid/vitamin B(12) treatment might promote more rapid progression.

Topics: Aged; Angioplasty, Balloon, Coronary; Biomarkers; Coronary Angiography; Coronary Artery Disease; Disease Progression; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Male; Middle Aged; Norway; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Observational studies have reported associations between circulating total homocysteine concentration and risk of cardiovascular disease. Oral administration of folic acid and vitamin B(12) can lower plasma total homocysteine levels.. To assess the effect of treatment with folic acid and vitamin B(12) and the effect of treatment with vitamin B(6) as secondary prevention in patients with coronary artery disease or aortic valve stenosis.. Randomized, double-blind controlled trial conducted in the 2 university hospitals in western Norway in 1999-2006. A total of 3096 adult participants undergoing coronary angiography (20.5% female; mean age, 61.7 years) were randomized. At baseline, 59.3% had double- or triple-vessel disease, 83.7% had stable angina pectoris, and 14.9% had acute coronary syndromes.. Using a 2 x 2 factorial design, participants were randomly assigned to 1 of 4 groups receiving daily oral treatment with folic acid, 0.8 mg, plus vitamin B(12), 0.4 mg, plus vitamin B(6), 40 mg (n = 772); folic acid plus vitamin B(12) (n = 772); vitamin B(6) alone (n = 772); or placebo (n = 780).. The primary end point was a composite of all-cause death, nonfatal acute myocardial infarction, acute hospitalization for unstable angina pectoris, and nonfatal thromboembolic stroke.. Mean plasma total homocysteine concentration was reduced by 30% after 1 year of treatment in the groups receiving folic acid and vitamin B(12). The trial was terminated early because of concern among participants due to preliminary results from a contemporaneous Norwegian trial suggesting adverse effects from the intervention. During a median 38 months of follow-up, the primary end point was experienced by a total of 422 participants (13.7%): 219 participants (14.2%) receiving folic acid/vitamin B(12) vs 203 (13.1%) not receiving such treatment (hazard ratio, 1.09; 95% confidence interval, 0.90-1.32; P = .36) and 200 participants (13.0%) receiving vitamin B(6) vs 222 (14.3%) not receiving vitamin B(6) (hazard ratio, 0.90; 95% confidence interval, 0.74-1.09; P = .28).. This trial did not find an effect of treatment with folic acid/vitamin B(12) or vitamin B(6) on total mortality or cardiovascular events. Our findings do not support the use of B vitamins as secondary prevention in patients with coronary artery disease.. clinicaltrials.gov Identifier: NCT00354081.

Topics: Aged; Aortic Valve Stenosis; Cardiovascular Diseases; Coronary Angiography; Coronary Artery Disease; Double-Blind Method; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Risk; Vitamin B 12; Vitamin B 6; Vitamin B Complex

A high level of total homocysteine (tHcy) is a risk marker for cardiovascular disease (CVD), and is related to inflammation. We wanted to test the effect of homocysteine-lowering B-vitamin therapy, as used in the Western Norway B-vitamin Intervention Trial (WENBIT), on inflammatory markers associated with atherosclerosis.. Single centre, prospective double-blind clinical interventional study, randomised in a 2 x 2 factorial design.. Ninety patients (21 female) with suspected coronary artery disease (CAD), aged 38-80 years, were blindly randomised into one of four groups of daily oral treatment with (A) folic acid (0.8 mg)/vitamin B12 (0.4 mg)/vitamin B6 (40 mg), (B) folic acid/vitamin B12, (C) vitamin B6 alone or (D) placebo. Blood samples were collected before and after 6 months of treatment.. Before intervention, median levels of the analytes were: tHcy 11.0 micromol L(-1), neopterin 8.1 nmol L(-1), soluble CD40 ligand (sCD40L) 3.9 ng mL(-1), interleukin (IL)-6 1.9 pg mL(-1), C-reactive protein (CRP) 1.9 mg L(-1) and low-density lipoprotein (LDL) cholesterol 3.3 mmol L(-1). tHcy was significantly associated with neopterin (r = 0.49, P < 0.001) and with IL-6 (r = 0.29, P = 0.01), but not with CRP or sCD40L. Neither treatment with folic acid/B12 nor with B6 induced significant changes in any of these inflammatory biomarkers (P >or= 0.14). In patients receiving folic acid/B12 (groups A and B), tHcy was reduced with 33% (P < 0.001).. In patients with stable CAD, homocysteine-lowering therapy with B-vitamins does not affect levels of inflammatory markers associated with atherogenesis. Failure to reverse inflammatory processes, may partly explain the negative results in clinical secondary B-vitamin intervention trials.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; CD40 Ligand; Cholesterol, LDL; Coronary Artery Disease; Double-Blind Method; Female; Folic Acid; Glomerular Filtration Rate; Homocysteine; Humans; Interleukin-6; Male; Middle Aged; Neopterin; Prospective Studies; Treatment Outcome; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Increased plasma total homocysteine (tHcy) levels are a risk factor for stroke and can be reduced with vitamin therapy. However, data on the tHcy-lowering effects of vitamins are limited largely to white populations. Thus, we aimed to determine in Singaporean patients with recent stroke: (1) the efficacy of vitamin therapy (folic acid, vitamin B12, and B6) on lowering tHcy, and (2) whether efficacy is modified by Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism(s).. A total of 443 eligible patients were recruited after presenting with ischemic stroke within the past 7 months. Patients were randomized to receive either placebo or vitamins. Fasting blood samples collected at baseline and at 1 year were assayed for levels of plasma tHcy. Patients were genotyped for MTHFR C677T and A1298C polymorphisms.. Mean baseline tHcy was similar in the 2 groups (placebo 13.7 micromol/L; vitamins 14.0 micromol/L; P=0.70). At 1 year, mean tHcy was 14.5 micromol/L in the placebo group compared with 10.7 micromol/L in the vitamin group (difference 3.8 micromol/L; 95% CI, 2.8 to 4.8 micromol/L; P<0.0001). MTHFR C677T genotype was an independent determinant of tHcy levels at baseline (P=0.005), but A1298C was not (P=0.08). Neither polymorphism significantly influenced the effect of vitamin therapy on tHcy at 1 year. The magnitude of the reduction in tHcy levels at 1 year with vitamin therapy was similar, irrespective of MTHFR genotypes.. Vitamin therapy reduces mean tHcy levels by 3.8 micromol/L in the Singaporean stroke population studied. MTHFR C677T but not A1298C is independently associated with tHcy levels at baseline, and neither impacts the tHcy-lowering effect of vitamins used in this study.

Topics: Aged; Coronary Artery Disease; Dietary Supplements; Female; Folic Acid; Follow-Up Studies; Genetic Predisposition to Disease; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Ischemic Attack, Transient; Male; Methylenetetrahydrofolate Dehydrogenase (NAD+); Middle Aged; Models, Statistical; Placebos; Polymorphism, Genetic; Regression Analysis; Risk Factors; Singapore; Stroke; Vitamin B 12; Vitamin B 6; Vitamins

Soy protein or its components may protect against the atherosclerotic cardiovascular disease (CVD) risk factors total homocysteine (tHcy), C-reactive protein (CRP), and excess body iron, which generally increase with menopause.. The primary objective of this study was to determine the independent effect of the soy protein components isoflavones and phytate on CVD risk factors in postmenopausal women. The secondary objective was to identify factors [blood lipids, oxidative stress indexes, serum ferritin, plasma folate, plasma vitamin B-12, and body mass index (BMI)] contributing to tHcy and CRP concentrations.. In a double-blind, 6-wk study, 55 postmenopausal women aged 47-72 y were randomly assigned to 1 of 4 soy protein (40 g/d) isolate treatments: native phytate and native isoflavone (n = 14), native phytate and low isoflavone (n = 13), low phytate and native isoflavone (n = 14), or low phytate and low isoflavone (n = 14). We measured iron indexes, tHcy, CRP, and BMI.. Soy protein with native phytate significantly reduced tHcy (P = 0.017), transferrin saturation (P = 0.027), and ferritin (P = 0.029), whereas soy protein with native isoflavones had no effect on any variables. At baseline, BMI was highly correlated with tHcy (r = 0.39, P = 0.003) and CRP (r = 0.55, P < 0.0001), whereas HDL cholesterol was correlated with CRP (r = -0.30, P = 0.02). Multiple regression analysis showed that LDL cholesterol and BMI contributed significantly (R2= 19.9%, P = 0.003) to the overall variance in tHcy.. Consuming phytate-rich foods and maintaining a healthy weight may reduce atherosclerotic CVD risk factors in postmenopausal women.

Topics: Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Coronary Artery Disease; Double-Blind Method; Female; Ferritins; Folic Acid; Homocysteine; Humans; Iron; Isoflavones; Lipids; Middle Aged; Oxidative Stress; Phytic Acid; Plant Proteins, Dietary; Postmenopause; Regression Analysis; Risk Factors; Soybean Proteins; Transferrin; Vitamin B 12

Elevated plasma levels of total homocysteine (tHcy) are associated with an increased risk of developing occlusive vascular diseases. To better illustrate the relationship between plasma tHcy concentration, oxidative stress, and inflammation in patients with coronary artery disease (CAD), we measured plasma 8-isoprostane-prostaglandin F 2 (Iso-P), plasma malondialdehyde (MDA), and several markers of inflammation. We also aimed to demonstrate the effects of vitamin supplementation on these markers.. A total of 93 patients with ischemic heart disease were investigated. Of these, 34 had plasma tHcy < or =8 micromol/L, while 59 had plasma tHcy > or = 15.0 micromol/L. The 59 patients were randomized to open therapy with folic acid, 5 mg, pyridoxine, 40 mg, and cyancobalamin, 1 mg once daily for 3 months (n = 29) or to no vitamin treatment (n = 30). Blood samples were obtained from both groups before randomization and 3 months later. A sample was also obtained from the remaining 34 patients.. Plasma Iso-P, serum amyloid A (S-AA), and plasma intercellular adhesion molecule-1 (ICAM-1) concentrations were higher in patients with high plasma tHcy levels than in patients with low to normal tHcy levels. Plasma levels of P-, L-, E-selectins, MDA, C-reactive protein (CRP), and orosomucoid did not differ between the groups. Vitamin therapy reduced plasma tHcy from 17.4 (15.3/20.1) to 9.2 (8.3/10.3) micromol/L (25th and 75th percentiles in parentheses) (p<0.0001). Plasma levels of Iso-P remained unchanged and, of all inflammatory markers, only the S-AA concentrations were slightly reduced by the vitamin treatment, from 5.3 (2.2/7.0) ng/L at baseline to 4.6 (2.1/6.9) ng/L (p<0.05) after 3 months of vitamin supplementation.. Patients with CAD and high plasma tHcy levels had elevated plasma levels of Iso-P. The increase remained unaffected by plasma tHcy-lowering therapy, suggesting that homocysteine per se does not cause increased lipid peroxidation. Levels of plasma ICAM-1 and S-AA were increased in patients with high plasma tHcy, suggesting an association between homocysteinemia and low-grade inflammation.

Topics: Aged; Biomarkers; Coronary Artery Disease; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Inflammation; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Pyridoxine; Vitamin B 12; Vitamins

To investigate whether vitamin B(6) supplementation had a beneficial effect on lowering fasting plasma homocysteine concentrations in coronary artery disease (CAD) patients.. A single-blind intervention study.. The study was performed at the Taichung Veterans General Hospital, the central part of Taiwan.. A total of 50 subjects were identified by cardiac catheterization to have at least 70% stenosis of one major coronary artery. In all, 42 patients successfully completed this study.. Patients were randomly assigned to one of five groups and treated with a daily dose of placebo (n=8), 5 mg vitamin B(6) (n=8), 10 mg vitamin B(6) (n=8), 50 mg vitamin B(6) (n=9), or 5 mg folic acid combined with 0.25 mg vitamin B(12) (n=9) for 12 weeks.. Nutrient intakes were recorded by using 24-h diet recalls when patients returned to the cardiology clinic before the intervention (week 0) and at week 12. Vitamin B(6) status was assessed by direct measures (plasma pyridoxal 5'-phosphate) and indirect measures (erythrocyte alanine and aspartate aminotransaminase activity coefficient). Fasting plasma homocysteine, serum folic acid, and vitamin B(12) were measured.. Fasting plasma homocysteine concentration did not respond to high or low doses of vitamin B(6) when compared with a placebo treatment after 12 weeks of supplementation. The mean fasting plasma homocysteine concentration, however, decreased significantly after 12 weeks of folic acid combined with vitamin B(12) supplementation (P=0.047). Further, within group, mean fasting plasma homocysteine concentration was nonsignificantly increased by 25.5, 16.2, and 18.3% in placebo, 10 mg/day and 50 mg/day vitamin B(6) supplemented groups, respectively; whereas folic acid combined with vitamin B(12) supplementation significantly reduced fasting plasma homocysteine concentration by 32% (P<0.001).. Our results indicate that vitamin B(6) supplementation alone is less effective than folic acid combined with vitamin B(12) in lowering plasma homocysteine concentrations in CAD patients.. This study was supported by the National Science Council, Taiwan, Republic of China (NSC-91-2320-B-040-023).

Topics: Adult; Aged; Aged, 80 and over; Coronary Artery Disease; Dose-Response Relationship, Drug; Female; Folic Acid; Homocysteine; Humans; Male; Mental Recall; Middle Aged; Single-Blind Method; Treatment Outcome; Vitamin B 12; Vitamin B 6

Cardiovascular diseases are the primary cause of mortality in France. Many epidemiological studies have shown that the total homocysteine concentration is a risk indicator for cardiovascular disease. Furthermore, it has been shown that the homocysteine concentration can be effectively lowered by supplementation with folic acid, vitamin B6 and B12. However, it is not yet known whether a reduction of the homocysteine concentration by such a supplementation indeed leads to a decreased risk of cardiovascular disease. Another possible dietary factor that may lower the risk of cardiovascular disease is fish-oil, which is rich in omega-3 fatty acids. These fatty acids lower platelet aggregation and triglyceride rich lipoproteins and may have antiarrhythmic effects. Some trials have investigated the effect of fish or fish-oil on cardiovascular mortality, and the results, although not conclusive, suggest a protective effect of a higher intake. In the SU.FOL.OM3 study we will evaluate the effect of supplementation at nutritional doses of folate (in the natural 5-methyl-tetrahydrofolate form) in combination with vitamin B6 and B12 and/or omega-3 fatty acids and/or placebo on recurrent ischemic diseases in a factorial design. The supplements will be randomly allocated to the participants in a double-blind fashion. In total 3,000 patients aged between 45 and 80 years who had a past history of myocardial infarction or unstable angina pectoris or an ischemic stroke will be included. The participants will be supplemented and followed up for a period of five years.

Topics: Aged; Aged, 80 and over; Coronary Artery Disease; Dietary Supplements; Double-Blind Method; Fatty Acids, Omega-3; Female; Folic Acid; Homocysteine; Humans; Intracranial Arteriosclerosis; Ischemia; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Secondary Prevention; Vitamin B 12; Vitamin B 6

Topics: Coronary Artery Disease; Folic Acid; Homocysteine; Humans; Prospective Studies; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Topics: China; Coronary Artery Disease; Folic Acid; Humans; Norway; Primary Prevention; Stroke; Uric Acid; Vitamin B 12; Vitamins

Topics: Coronary Artery Disease; Folic Acid; Humans; Uric Acid; Vitamin B 12; Vitamins

Observationally, homocysteine is positively associated with ischemic heart disease (IHD) and unhealthy lipids; folate and vitamin B12, which reduce homocysteine, are associated with lower IHD risk and healthy lipids. Randomized controlled trials have shown no benefits of folate and vitamin B12 for IHD. To clarify the role of these potential targets of intervention in IHD we assessed how genetically determined homocysteine, folate and vitamin-B12-affected IHD and lipids.. Separate-sample instrumental variable analysis with genetic instruments, that is, Mendelian randomization, was used to obtain unconfounded estimates (based on strongly related single-nucleotide polymorphisms (SNPs)) using CARDIoGRAMplusC4D, a large coronary artery disease/myocardial infarction (CAD/MI) case (n=64 374)-control (n=130 681) study with extensive genotyping, and the Global Lipids Genetics Consortium Results (n=196 475).. Homocysteine was unrelated to CAD/MI (odds ratio (OR) 1.07 per log-transformed s.d., 95% confidence interval (CI) 0.96 to 1.19) based on 14 SNPs, as was folate (OR 1.18 per s.d., 95% CI 0.80 to 1.75) based on rs153734, and vitamin B12 (OR 0.98 per log-transformed s.d., 95% CI 0.85 to 1.14) based on rs602662, rs9473555, rs526934 and rs11254363. Homocysteine and folate were not clearly associated with lipids, vitamin B12 was associated with higher inverse normal transformed low-density lipoprotein cholesterol (0.07, 95% CI 0.02 to 0.12) and triglycerides (0.05, 95% CI 0.004 to 0.09).. Our findings do not corroborate the observed positive association of homocysteine or negative associations of folate and vitamin B12 with CAD/MI. Vitamin B12 might be associated with an unfavorable lipid profile.

Topics: Adult; Aged; Case-Control Studies; Coronary Artery Disease; Female; Folic Acid; Genotype; Homocysteine; Humans; Male; Mendelian Randomization Analysis; Middle Aged; Myocardial Infarction; Odds Ratio; Polymorphism, Single Nucleotide; Vitamin B 12; Vitamin B Complex

Homocysteine (Hcy) has been considered as an independent risk factor for coronary artery disease (CAD). Folic acid and vitamin B. Serum Hcy, folic acid and vitamin B. Compared to SAP patients, patients with AMI and UAP had higher Hcy levels with approximately average elevated (4-5) μmol/L, while SAP patients were approximately higher 8 μmol/L than controls. However, the levels of folic acid and vitamin B. The present study provide the valuable evidence that high concentrations of Hcy and low levels of folic acid and vitamin B

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; China; Coronary Artery Disease; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Incidence; Male; Middle Aged; Prevalence; Retrospective Studies; Risk Factors; Severity of Illness Index; Vitamin B 12

Coronary artery disease (CAD) has been increasing alarmingly in India. We had earlier shown that vitamin B12 deficiency is associated with CAD in Indian population. However, only about a quarter of the total vitamin B12 is internalised in the cells by the proteins transcobalamin II. Vitamin B12-bound transcobalamin II (holotranscobalamin, holoTC) is thus referred to as biologically active B12. In this study, we ascertained the levels of holoTC in 501 CAD cases and 1253 healthy controls and for the first time show that holoTC levels are significantly lower (p = 2.57E-4) in CAD (26.81 pmol/l) cases as compared to controls (29.97 pmol/l).

Topics: Asian People; Case-Control Studies; Coronary Artery Disease; Humans; India; Prevalence; Transcobalamins; Vegetarians; Vitamin B 12

Folate and vitamin B12 are essential components in the metabolism of homocysteine (Hcy). Hyperhomocysteinemia has been implicated in endothelial dysfunction and cardiovascular disease. However, the association of Hcy, vitamin B12, and folic acid with cardiovascular risk factors in patients with coronary artery disease (CAD) has not been studied in Indian patients. This study was conducted with the aim to evaluate the relationship of vitamin B12, folic acid, and Hcy levels with cardiovascular risk factors in subjects with known CAD.. Three hundred patients (216 men; 84 women; aged 25-92 years) who had CAD on angiography were included in this study consecutively. All patients were evaluated for anthropometry and cardiovascular risk factors, and blood samples were collected for biochemical, nutritional, and inflammatory markers.. Percentage of vitamin B12 and folate deficiency was 86.7% and 2.7%, respectively. Hyperhomocysteinemia was present in 95.3% patients. Vitamin B12 levels were significantly lower and Hcy levels were significantly higher in subjects with dyslipidemia, DM, and/or hypertension. Serum vitamin B12 was inversely associated with triglyceride and very low-density lipoprotein (VLDL) and positively with high-density lipoprotein (HDL). Hcy was positively associated with triglyceride and VLDL and negatively with HDL. Vitamin B12 was inversely correlated with inflammatory markers (high-sensitivity C-reactive protein and interleukin-6) directly related to insulin resistance whereas Hcy showed the opposite pattern.. Serum vitamin B12 deficiency and hyperhomocysteinemia are related with cardiovascular risk factors in Indian patients with CAD.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Coronary Artery Disease; Dyslipidemias; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; India; Male; Middle Aged; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

Transcobalamin (TCII) is a key enzyme involved in intracellular transport of vitamin B12. We had earlier shown that vitamin B12 levels are associated with Coronary Artery Disease (CAD). Herein, we evaluated the association of four nonsynonymous single nucleotide polymorphisms (SNPs) of TCII gene with CAD in 1398 individuals (589 CAD cases and 809 controls). Using logistic regression, we found that three SNPs (G1196A, C776G and C1043T) were significantly associated with CAD and one (G1196A) with vitamin B12 levels even after controlling for confounding factors. Thus, polymorphisms in TCII gene may play an important role in the etiology of CAD.

Topics: Adult; Alleles; Case-Control Studies; Coronary Artery Disease; Female; Gene Frequency; Genotype; Humans; India; Male; Middle Aged; Polymorphism, Single Nucleotide; Regression Analysis; Transcobalamins; Vitamin B 12; White People

Hyperhomocysteinaemia (HCA) either due to mutation of MTHFR gene or deficiency of vitamin B 12 and folic acid, has been reported as a risk factor for coronary artery disease (CAD). The present study was aimed to determine plasma homocysteine (Hcy) levels and to evaluate MTHFR C677T gene polymorphism as risk factors for CAD, and to study the role of Hcy in conjunction with a few other risk factors of CAD in young Indians. The effect of vitamin B12 and folic acid supplements on the raised plasma Hcy levels in patients of CAD was also assessed.. The present study included 199 consecutive angiography confirmed CAD patients, <45 yr of age, without any other known pro- coagulant state and 200 age- and sex-matched healthy controls. Fasting blood samples were collected in EDTA and plasma Hcy was estimated by ELISA test and the MTHFR C677T polymorphism detection was carried out by PCR-RFLP method.. Significant difference (P<0.001) was found between mean fasting levels of plasma Hcy in cases (22.14 ± 10.62 μmol/l) and controls (17.38 ± 8.46 μmol/l) with an Odds ratio as 1.93 (95% CI, 1.27-2.94). Levels of cholesterol, LDL, and triglycerides were significantly (P<0.001) higher in cases compared with controls.. Our study showed significant correlation between hyperhomocysteinaemia and coronary artery disease. Multivariate analysis by logistic regression of the various risk factors of CAD, found high levels of Hcy, cholesterol, LDL and low levels of HDL and smoking as independent predictors of CAD when all other factors were controlled. Significant post-treatment decrease found in HCA was easily modifiable by vitamin intervention irrespective to their CT or TT genotype of C677T MTHFR gene. Further studies to look at the plasma levels of folate and cobalamines and their association with Hcy are required to be done.

Topics: Adult; Cholesterol; Coronary Artery Disease; Female; Folic Acid; Genetic Association Studies; Homocysteine; Humans; Hyperhomocysteinemia; India; Lipoproteins, HDL; Lipoproteins, LDL; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic; Risk Factors; Smoking; Triglycerides; Vitamin B 12

Methylenetetrahydrofolate reductase (MTHFR) C677T is involved in folate and homocysteine metabolism. Disruption in the activity of this enzyme will alter their levels in the body.. This study assessed MTHFR C677T polymorphism and its relationship with serum homocysteine and B-vitamins levels in a sample of Chinese and Malays subjects in UPM, Serdang. One hundred subjects were randomly selected from among the university population. Folate, vitamin B12, B6, and homocysteine levels were determined using MBA, ECLIA, and HPLC, respectively. PCR coupled with HinfI digestion was used for detection of MTHFR C677T polymorphism.. The frequency of T allele was higher in the Chinese subjects (0.40) compared to the Malay (0.14). Folate, vitamin B12 and B6 levels were highest in the wild genotype in both ethnic groups. Subjects with heterozygous and homozygous genotype showed the highest homocysteine levels. The serum folate and homocysteine were mainly affected by homozygous genotype.. MTHFR C677T polymorphism plays an important role in influencing the folate and homocysteine metabolism.

Topics: Adult; Asian People; Coronary Artery Disease; Cross-Sectional Studies; DNA; DNA Primers; Female; Homocysteine; Humans; Malaysia; Male; Methylenetetrahydrofolate Reductase (NADPH2); Polymerase Chain Reaction; Polymorphism, Genetic; Students; Vitamin B 12; Young Adult

Moderate hyperhomocysteinaemia is considered as an independent risk marker for cardiovascular disease and stroke. Earlier, increased homocysteine production was detected in stimulated immunocompetent cells in vitro, and several markers of inflammation like neopterin or C-reactive protein (CRP) were demonstrated as significant indicators of cardiovascular risk. The relationship between coronary artery disease (CAD), homocysteine metabolism and markers of immune activation and inflammation was investigated in a population of 1717 patients undergoing coronary angiography, recruited as participants of the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study. 1325 patients (77.2%) suffered from coronary artery disease (CAD), which was was defined as the occurrence of a visible luminal narrowing (>or=20% stenosis) in at least 1 of 15 coronary segments according to the classification of the American Heart Association, the remaining 392 individuals of the study population served as controls. Significant differences regarding systolic blood pressure, homocysteine, neopterin and folic acid concentrations were observed between patients and controls. Older age, decreased creatinine-clearance and higher concentrations of homocysteine and CRP were indicative for CAD. Low B-vitamin availability, therapy and the extent of immune activation strongly influenced homocysteine concentrations. Homocysteine concentrations were correlated with neopterin levels (r(s) =0.325, p<0.001), and hyperhomocysteinaemic patients also presented with significantly higher CRP concentrations. Homocysteine accumulation coincided with impaired renal and heart function (as reflected by ProBNP[Brain natriuretic peptide]-concentrations). We conclude that homocysteine accumulation could result from B-vitamin deficiency which is related to chronic immune activation.

Topics: Aged; Biomarkers; C-Reactive Protein; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Creatinine; Disease Progression; Female; Folic Acid; Homocysteine; Humans; Inflammation Mediators; Male; Middle Aged; Neopterin; Vitamin B 12

Topics: Adrenergic beta-Antagonists; Calcium Channel Blockers; Coronary Artery Disease; Dilatation, Pathologic; Diltiazem; Female; Folic Acid; Homocysteine; Humans; Male; Metoprolol; Middle Aged; Treatment Outcome; Vitamin B 12

The aim of the present study was to investigate the association between genetic variants in metylenetetrahydrofolate reductase (MTHFR) and Paraoxonase-1 (PON1) 55/192 genes and total homocysteine (tHcy), folate, B12 vitamin, and PON1 levels in patients with coronary artery disease (CAD).. The study included 235 patients with CAD and 268 healthy control subjects.. LL and LM genotypes and L allele of PON1 55 were over-represented in patients. In contrast, MM genotype and M allele were more frequent in controls. QQ genotype and Q allele of PON1 192 and CT genotype of MTHFR were significantly diminished and QR genotype and R allele were significantly elevated in CAD patients compared with controls. The plasma tHcy were elevated but B12 levels were diminished in patients. PON1 55 and 192 genetic variants were significantly associated with PON1 activity, triglyceride, total cholesterol, tHcy and, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol in patients, respectively.. Genetic variants of PON1 55/192 and MTHFR were associated with CAD.

Topics: Aged; Aryldialkylphosphatase; Coronary Artery Disease; Female; Folic Acid; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Vitamin B 12

The increase of circulating asymmetric dimethylarginine (ADMA) concentrations, a competitive inhibitor of the nitric oxide synthases, is associated with an increased cardiovascular risk and is considered to play a role in endothelial dysfunction. Recently, ADMA production was observed in stimulated human peripheral mononuclear cells. In this study, we examined a potential relationship between concentrations of ADMA and of the immune activation marker neopterin in patients scheduled for coronary angiography. In a cross-sectional approach, blood concentrations of ADMA, homocysteine, neopterin, folic acid and vitamins B6 and B12 were compared in 2030 patients, which were recruited as participants of the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study. ADMA concentrations did not differ between patients with coronary artery disease (CAD) (mean +/- SD: 0.82 +/- 0.15 micromol/l) and controls (0.81 +/- 0.14 micromol/l; Welch's t-test: P = n.s.). ADMA concentrations correlated with homocysteine (r(s) = 0.207) and vitamin B6 (r(s) = -0.190), and an even stronger correlation with neopterin (r(s) = 0.276; all P < 0.0001) was observed. In conclusion, increased ADMA concentrations in patients at risk for atherosclerosis are associated with increased neopterin concentrations. Data suggest that immune activation may contribute to increased ADMA production in CAD patients.

Topics: Arginine; Chromatography, High Pressure Liquid; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Folic Acid; Homocysteine; Humans; Middle Aged; Neopterin; Risk Factors; Vitamin B 12; Vitamin B 6

Hyperhomocysteinemia is an independent risk factor for coronary artery disease (CAD). The aim of this study was to investigate the relations between the methylenetetrafolate reductase (MTHFR) 677C-->T genotypes, B-vitamins (folate, vitamin B-12 and B-6), homocysteine and the risk of CAD. In this case-control study, patients who were identified by cardiac catheterization as having at least 50% stenosis of one major coronary artery were assigned to the case group (n=121). Healthy individuals with normal blood biochemical values were assigned to the control group (n=155). Healthy subjects were matched to case subjects for age. The concentrations of plasma homocysteine, serum folate, vitamin B-12, plasma pyridoxal 5'- phosphate (PLP) and MTHFR 677C-->T gene polymorphism were obtained. The T-allele carriers had significantly higher plasma homocysteine concentration compared to subjects with the 677CC genotype. The MTHFR 677C-->T genotypes were associated with plasma homocysteine after adjusting for various potential risk factors in the case and pooled groups. The MTHFR genotypes were found to have no associations with the risk of CAD. However, plasma homocysteine (>or= 12.5 micromol/L) (OR, 3.49; 95% CI, 1.23-9.88) had a significant association with increased risk of CAD even after additionally adjusted folate status. High plasma homocysteine concentration had a direct effect on the risk of CAD independent of MTHFR 677C-->T genotypes.

Topics: Alleles; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Female; Folic Acid; Genetic Predisposition to Disease; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic; Risk Factors; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Topics: Aged; Aortic Valve Stenosis; Cardiovascular Diseases; Coronary Angiography; Coronary Artery Disease; Double-Blind Method; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk; Survival Analysis; Survival Rate; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Previous studies have shown conflicting results regarding circulating homocysteine levels in patients with type 2 diabetes.. This observational study included 2121 patients with angiographically proven coronary artery disease (507 patients with type 2 diabetes and 1614 patients without diabetes). Circulating homocysteine levels, methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, renal function, presence of coronary artery disease (CAD) diagnosed by coronary angiography, and circulating folate and vitamin B12 status were assessed. Plasma homocysteine levels [median (25th; 75th percentile)] were significantly higher in patients with diabetes than in those without [12.4 micromol/L (9.9 micromol/L; 15.9 micromol/L) versus 11.7 micromol/L (9.6 micromol/L; 14.5 micromol/L), P=0.011]. Diabetes affected homocysteine levels only in patients with a glomerular filtration rate <90 mL/min [13.0 micromol/L (10.5 micromol/L; 16.7 micromol/L) in patients with diabetes versus 12.2 micromol/L (10.1 micromol/L; 15.2 micromol/L) in patients without diabetes, P=0.006] but not in those with a glomerular filtration rate > or = 90 mL/min [10.1 micromol/L (8.1 micromol/L; 12.4 micromol/L) versus 10.2 micromol/L (8.8 micromol/L; 12.3 micromol/L), P=0.267]. Multivariable analysis did not show an independent association between diabetes and homocysteine level (P=0.342).. Circulating homocysteine levels are increased in patients with type 2 diabetes compared with non-diabetic patients due to a more diabetes-associated adverse risk profile rather than to diabetes itself.

Topics: Aged; Blood Glucose; Coronary Angiography; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Folic Acid; Genotype; Glomerular Filtration Rate; Glycated Hemoglobin; Homocysteine; Humans; Linear Models; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Multivariate Analysis; Polymorphism, Genetic; Up-Regulation; Vitamin B 12

Essential hypertension (EH) and cardiovascular disease are common, multifactorial disorders likely to be influenced by multiple genes of modest effect. The C677T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism is related to MTHFR enzyme activity and to plasma homocysteine (Hcy) concentration. This study was designed to investigate an association of this polymorphism with coronary artery disease (CAD), EH, and healthy subjects.. In this study, we measured serum folate, serum vitamin B12, and plasma homocysteine and determined the MTHFR C677T genotype of 78 patients with essential hypertension, 100 patients with coronary artery disease, and 100 healthy subjects. MTHFR genotypes were assessed by real-time polymerase chain reaction.. CC, CT, and TT genotype frequencies were 52, 44.0, and 4.0% in patients with CAD, respectively. In patients with essential hypertension, the CC, CT, and TT genotype frequencies were 46.2, 41.0, and 12.8%, respectively. In control subjects, the CC, CT, and TT genotype frequencies were 72.0, 26.0, and 2.0%, respectively. The C allele was significantly more frequent in controls compared with patients with EH (p<0.05), and CC genotypes were more frequent in controls compared to patients with EH and CAD. Homocysteine level was higher in TT genotypes in CAD patients compared with CC and CT genotypes (p<0.01). MTHFR gene polymorphism is an independent risk factor for EH but not for CAD.. The TT genotype of the 677C/T MTHFR polymorphism is associated with EH and CAD. In addition, TT genotypes had higher plasma Hcy levels in CAD patients compared with CC and CT genotypes. MTHFR gene polymorphism is an independent risk factor for EH but not for CAD.

Topics: Aged; Coronary Artery Disease; Female; Folic Acid; Gene Frequency; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Hypertension; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic; Risk Factors; Turkey; Vitamin B 12

Obesity and homocysteine are important risk factors for cardiovascular disease. The relation between pattern of obesity and homocysteine is unclear. The objective of this study was to investigate the relation between pattern of obesity and plasma total homocysteine (tHcy) level in male patients with coronary artery disease (CAD).. A total of 63 male patients (mean age 66.2 years) with angiographically documented CAD were enrolled. Overnight fasting blood samples were measured for plasma tHcy, serum folic acid and serum vitamin B12 levels. Anthropometric measurements included waist-to-hip ratio (WHR) and body mass index (BMI).. The mean WHR was 0.90+/-0.05, mean BMI 24.6+/-3.3 kg/m2 and the mean plasma tHcy level 11.6+/-3.2 micromol/L. In univariate analysis, plasma tHcy level correlated significantly with serum vitamin B12 level, serum folic acid level, WHR, estimated creatinine clearance, aspirin use and fibrate use. There was no significant association between plasma tHcy level and BMI. In multivariate analysis, only WHR (beta-value 22.263, p<0.001), serum level of vitamin B12 (beta-value -0.004, p=0.003), estimated creatinine clearance (beta-value -4.154, p=0.003) and use of fibrates (beta-value 2.307, p=0.031) were independent predictors of plasma tHcy level.. WHR, but not BMI, is a strong independent predictor of plasma tHcy level in male patients with CAD.

Topics: Aged; Biomarkers; Body Mass Index; Coronary Artery Disease; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Obesity; Risk Factors; Vitamin B 12; Waist-Hip Ratio

Hyperhomocysteinemia confers an increased risk of coronary artery disease, stroke, and deep vein thrombosis, and is a strong predictor of mortality among patients with ischemic heart disease.. To determine the long term clinical outcome of patients with risk factors to atherosclerosis with high concentrations of homocysteine (Hcy).. 89 patients with one or more risk factors for atherosclerosis, whose plasma total Hcy concentrations were measured, were followed for 5 years. Patients were interviewed and underwent a clinical examination in the outpatient clinic. Their medical records were reviewed in the last 5 years including smoking habits, medications, other diseases (hypertension, diabetes mellitus, hyperlipidemia) and their management. SPSS was used to describe and explore possible relationships between Hcy concentration, other diseases, medications and the clinical long term outcome.. All men with normal Hcy concentrations (10.76+/-1.71 micromol/L) survived during the 5 years' follow up, while 5 of the men with high Hcy concentrations (21.27+/-5.37 micromol/L), died (17%) (P< 0.05). In women Hcy concentration did not affect survival. No association was found between diabetes mellitus, hypercholesterolemia, hypertension and Hcy. Long term treatment with Beta Blockers, ACE inhibitors, Calcium Channel blockers, and especially with Aspirin prevented death and changed the natural history of patients with high Hcy concentrations (P < 0.05).. Hyperhomocysteinemia may have an effect on survival in men. Long term treatment with Beta Blockers, ACE inhibitors, Calcium Channel Blockers, and especially with Aspirin--prevented death and changed the natural history of patients with high Hcy concentrations.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Atherosclerosis; Coronary Artery Disease; Enzyme-Linked Immunosorbent Assay; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Prospective Studies; Risk Factors; Sex Factors; Time Factors; Treatment Outcome; Vitamin B 12; Vitamin B Complex

Elevated plasma total homocysteine is a major risk for coronary artery disease (CAD). Methyltetrahydrofolate reductase (MTHFR) is a main regulatory enzyme in homocysteine metabolism; a common C677T mutation in the MTHFR gene results in decreased enzyme activity, and contributes to increased homocysteine levels and decreased folate levels. We investigated the frequency of MTHFR C677T alleles in a Korean population, determined the genotype-specific threshold levels of folate or vitamin B12, and investigated the relationship between the TT genotype and the risk of CAD.. We enrolled a study population of 163 CAD patients and 50 control subjects, and screened the MTHFR C677T polymorphism using real-time PCR with melting point analysis. Levels of plasma homocysteine, folate and vitamin B12 were also determined. We then defined the genotype-specific threshold values of folate and vitamin B12 required to keep homocysteine levels in a normal range for individuals of each MTHFR C677T genotype.. The frequency of the TT genotype was 18% in control subjects and 26% in patients group (P>0.05). Individuals homozygous for the TT genotype had significantly elevated homocysteine levels (P<0.05). The genotype-specific folate threshold level was significantly higher in TT individuals than in the CC or CT genotypes. The OR of individuals with low folate status and the TT genotype to estimate the relative risk of CAD was 2.2 and the OR of those with high folate status and the TT genotype was 1.5 (95% CI, 0.5-9.6 and 0.7-3.2, respectively).. We were able to define a gene-nutrient interaction that shows a higher risk for CAD based on specific threshold folate levels required by different MTHFR C677T genotypes in a Korean population.

Topics: Adult; Aged; Aged, 80 and over; Alleles; Coronary Artery Disease; Female; Folic Acid; Genotype; Homocysteine; Humans; Korea; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Nutritional Status; Polymorphism, Genetic; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Vitamin B 12

Topics: Coronary Artery Disease; Homocysteine; Humans; Hyperhomocysteinemia; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Genetic; Stroke; Vitamin B 12

Individuals with Type 2 diabetes are at increased risk of stroke. Plasma homocysteine (tHcy) is an independent risk factor for cardiovascular (CV) disease. The methylene-tetrahydrofolate reductase (MTHFR) gene polymorphism (thermolabile variant C(677)T) is associated with CV risk, partly as a result of increased Hcy, especially in homozygous subjects.. To relate the occurrence of the MTHFR polymorphism with stroke prevalence by examining allelic frequency and genotype distribution in 165 subjects with Type 2 diabetes studied for the presence of thermolabile C(677)T MTHFR mutation.. Mean age was 67.7 years, and tHcy 18.2 micromol/l. T allele frequency was 38.5%. MTHFR genotypes were: normal (CC) 40%; heterozygous (CT) 43%; homozygous (TT) 17%. Serum levels of folic acid and B12 vitamin were within normal limits. Stroke prevalence was 14%. Sixty-four per cent of stroke-free subjects had the normal C allele vs. 46% in stroke subjects. The frequencies of genotypes (CC-CT-TT) were (%): 44-41-15 in stroke-free vs. 17-57-26 in stroke patients. Coronary (CAD) and peripheral artery disease (PAD) were common in all groups, with no differences according to genotypes. Stroke prevalence was markedly higher in genotypes CT and TT (18 and 21%) compared with CC (6%). Mean tHcy levels were higher in TT subjects.. The allelic frequency of C(677)T MTHFR mutation in Type 2 diabetes subjects with stroke is markedly different from that of subjects without stroke. Genotypic characteristics suggest that C(677)T MTHFR mutation confers a higher risk for stroke to both homozygous and heterozygous T allele carriers that cannot be ascribed solely to raised tHcy and/or lower folate status in CT subjects, nor to phenotypic expression of conventional risk factors for stroke. The impact of the MTHFR polymorphism on stroke may result from T allele-linked deleterious effects, or C allele-linked protection. Confirmatory studies are warranted, as this cohort was not randomly selected, and a type 1 error cannot be ruled out.

Topics: Aged; Cohort Studies; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Folic Acid; Gene Frequency; Heterozygote; Homozygote; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Mutation; Peripheral Vascular Diseases; Polymorphism, Genetic; Risk Factors; Stroke; Vitamin B 12

Hyperhomocysteinemia is known as an independent risk factor of atherosclerosis, but the probable role of hyperhomocysteinemia in premature Coronary Artery Disease (CAD) is not well studied. The aim of this study was to assess the role of hyperhomocysteinemia, folate and Vitamin B12 deficiency in the development of premature CAD.. We performed an analytical case-control study on 294 individuals under 45 years (225 males and 69 females) who were admitted for selective coronary angiography to two centers in Tehran.. After considering the exclusion criteria, a total number of 225 individuals were enrolled of which 43.1% had CAD. The mean age of participants was 39.9 +/- 4.3 years (40.1 +/- 4.2 years in males and 39.4 +/- 4.8 years in females). Compared to the control group, the level of homocysteine measured in the plasma of the male participants was significantly high (14.9 +/- 1.2 versus 20.3 +/- 1.9 micromol/lit, P = 0.01). However there was no significant difference in homocysteine level of females with and without CAD (11.8 +/- 1.3 versus 11.5 +/- 1.1 micromol/lit, P = 0.87). Mean plasma level of folic acid and vitamin B12 in the study group were 6.3 +/- 0.2 and 282.5 +/- 9.1 respectively. Based on these findings, 10.7% of the study group had folate deficiency while 26.6% had Vitamin B12 deficiency. Logistic regression analysis for evaluating independent CAD risk factors showed hyperhomocysteinemia as an independent risk factor for premature CAD in males (OR = 2.54 0.95% CI 1.23 to 5.22, P = 0.01). Study for the underlying causes of hyperhomocysteinemia showed that male gender and Vitamin B12 deficiency had significant influence on incidence of hyperhomocysteinemia.. We may conclude that hyperhomocysteinemia is an independent risk factor for CAD in young patients (below 45 years old)--especially in men--and vitamin B12 deficiency is a preventable cause of hyperhomocysteinemia.

Topics: Adult; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; Male; Prevalence; Risk Factors; Sex Characteristics; Vitamin B 12; Vitamin B 12 Deficiency

Hyperhomocysteinemia is recognized as an independent risk factor for arterial disease including coronary artery disease, cerebrovascular disease and peripheral vascular disease. Previously, an association between increased plasma homocysteine level and peripheral arterial aneurysms has been reported. However, the relationship between coronary artery ectasia (CAE) and plasma homocysteine level has not been investigated. Accordingly, this study was designed to investigate plasma homocysteine level in patients with isolated CAE.. Thirty-two patients with isolated CAE without significant stenosis and 30 control subjects with angiographically normal coronary arteries were included in this study. Fasting plasma homocysteine concentrations were measured by Fluorescence Polarization Immunoassay method using homocysteine kids. Hyperhomocysteinemia is defined as plasma homocysteine levels above the 95th percentile of the control subjects (13.6 mumol/l).. According to the definition of hyperhomocysteinemia, 19 (59%) of patients with isolated CAE had elevated levels of plasma homocysteine compared to 2 (7%) in the control subjects with angiographically normal coronary arteries (p<0.001). In addition, patients with isolated CAE had significantly higher levels of plasma homocysteine compared to control subjects (14.9+/-4.5 micromol/l vs. 8.6+/-1.9 micromol/l respectively, p<0.001). Besides, we detected a significant positive correlation between the number of ectasic segment and plasma homocysteine level (r=0.537, p=0.002).. We have shown for the first time an association between elevated plasma homocysteine level and isolated CAE. Larger prospective studies are needed to confirm the role of hyperhomocysteinemia in CAE and to evaluate the usefulness of homocysteine-lowering therapies.

Topics: Biomarkers; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Dilatation, Pathologic; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Prospective Studies; Vitamin B 12

Elevated plasma total homocysteine (tHcy) predisposes to vascular disease and results from interactions between genetic and nutritional factors. MTHFR C(677)T increases tHcy in association with low folate. CBS 844ins68 lowers tHcy and negates the raising effect of MTHFR C(677)T in healthy subjects, but it is unclear if this is the case in subjects at high risk of vascular disease. This study examines the effect on plasma tHcy of interactions between these polymorphisms in an at-risk group.. Blood samples were collected from 376 subjects at increased risk of coronary artery disease. Plasma tHcy and vitamin B(6) were measured by HPLC and red cell folate and serum vitamin B(12) were measured by immuno-luminometric assay. MTHFR C(677)T and CBS 844ins68 status was established by standard PCR techniques.. MTHFR TT predisposed to hyperhomocysteinaemia; this was increased in the presence of low folate (P<0.05) and vitamin B(12) (P<0.01). An inverse relationship was found between tHcy and folate (r=-0.42, P<0.0001), vitamin B(12) (r=-0.26, P<0.0005) and vitamin B(6) (r=-0.25, P<0.01). There was no interaction between plasma tHcy, vitamins or MTHFR C(677)T and CBS 844ins68.. In this population at high risk of coronary artery disease, plasma tHcy was determined by vitamin status. This was exacerbated by the MTHFR C(677)T mutation. CBS 844ins68 did not influence tHcy and did not negate the tHcy-raising effect of MTHFR C(677)T.

Topics: 5,10-Methylenetetrahydrofolate Reductase (FADH2); Coronary Artery Disease; Cystathionine beta-Synthase; Environment; Erythrocytes; Female; Folic Acid; Genetic Predisposition to Disease; Homocysteine; Humans; Male; Polymorphism, Genetic; Risk Factors; Vitamin B 12; Vitamin B 6

Methylenetetrahydrofolate reductase polymorphism (MTHFR C677T) is an established determinant of homocysteine plasma level (t-Hcys) while its association with coronary artery disease (CAD) seems to be more limited. In contrast, the association of the substitutions A2756G of methionine synthase (MTR), A66G of methionine synthase reductase (MTRR) and C776G of transcobalamin (TCN) to both t-Hcys and CAD needs to be evaluated further. The objective was to evaluate the association of these polymorphisms with t-Hcys and CAD in a French population. We investigated the individual and combined effects of these polymorphisms and of vitamin B12 and folates with t-Hcys in 530 CAD patients and 248 matched healthy controls. t-Hcys was higher in the CAD group than in controls (11.8 vs 10.4 microM, P < 0.0001) and in carriers of MTRRAA and MTHFR 677TT than in those carrying the most frequent allele of both polymorphisms (13.8 vs 11.4 microM, P = 0.0102 and 12.5 vs 11.0 mM, P = 0.0065 respectively). The frequency of MTRR A allele was higher in CAD patients than in controls (0.48 [95% CI: 0.44-0.52] vs 0.38 [95% CI: 0.32-0.44], P = 0.0081) while no difference was observed for MTHFR 677T frequency. In multivariate analysis, t-Hcys > median and MTRRAA genotype were two significant independent predictors of CAD with respective odds ratios of 3.1 (95 % CI: 1.8-5.1, P < 0.0001) and 4.5 (95% CI: 1.5-13.1, P = 0.0051). In conclusion, in contrast to North Europe studies, MTRRAA genotype is a genetic determinant of moderate hyperhomocysteinemia associated with CAD in a French population without vitamin fortification.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Aged; Alleles; Case-Control Studies; Coronary Artery Disease; Female; Ferredoxin-NADP Reductase; Folic Acid; France; Genetic Predisposition to Disease; Genotype; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic; Transcobalamins; Vitamin B 12; White People

The aim of the study was to evaluate the concentration and distribution of homocysteine in random samples of men and women aged 20-74 from two populations: urban (Warsaw) and industrial-rural (former Tarnobrzeg Province), and the estimation of relationship between selected cardiovascular risk factors and homocysteine concentration. In 2001 in 617 men and 657 women homocysteine level, lipids profile, glucose, folic acid, vitamin B12 concentration, blood pressure and alcohol intake were determined. The mean (geometric) homocysteine concentration was 10.9 micro mol/L in men and 9.6 micro mol/L in women. There were no differences in the homocysteine concentration and distribution between regions according to sex. The homocysteine level was connected with folic acid and vitamin B12 concentration in both genders. Moreover, in men was recorded relationship between homocysteine and body mass index, cholesterol level, alcohol intake, and in women between homocysteine and daily number of cigarettes smoked.

Topics: Adult; Aged; Coronary Artery Disease; Environmental Monitoring; Epidemiological Monitoring; Female; Folic Acid; Health Status; Homocysteine; Humans; Life Style; Male; Middle Aged; Poland; Risk Factors; Rural Population; Smoking; Urban Population; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Many traditional independent risk factors such as diabetes mellitus, hypertension, hypercholesterolaemia, smoking, male sex, old age, etc., contribute to the development of coronary artery disease (CAD). Hyperhomocysteinaemia is an independent risk factor of CAD but the role of plasma homocysteine (Hcy) in high risk patients (> or = 3 risk factors) is not known. We investigated the role of plasma Hcy, folic acid, vitamin B12 in patients with high risk (> or = 3 risk factors) of CAD and effects of supplementation of folic acid in the patients with hyperhomocysteinaemia.. The plasma Hcy levels in 152 patients with > or = 3 risk factors of CAD and 136 patients with 1-2 risk factors and 48 individuals with no risk factors were measured using high performance liquid chromatography (HPLC) with fluorescence detection. Plasma folic acid and vitamin B12 levels were also measured in these patients with immunoassays. The patients with hyperhomocysteinaemia were treated with 5 mg of folic acid for 8 wk, and plasma levels of Hcy were measured after treatment.. The plasma Hcy level was significantly higher in the patients with > or = 3 risk factors of CAD than in those with 1-2 risk factors and controls. The plasma levels of folic acid and vitamin B12 were significantly lower in the patients with > or = 3 risk factors of CAD compared to those with 1-2 risk factors and controls. The Hcy levels in the patients with > or = 3 risk factors of CAD significantly reduced by 33.5 per cent after 8 wk folic acid administration.. Plasma Hcy level was elevated significantly in patients with > or = 3 risk factors of CAD. Hyperhomocysteinaemia appears to play an important role in the pathogenesis of CAD. Folic acid supplementation may be useful in reducing plasma Hcy level in high risk patients with hyperhomocysteinaemia.

Topics: Adult; Aged; Chromatography, High Pressure Liquid; Coronary Artery Disease; Dietary Supplements; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Immunoassay; Male; Microscopy, Fluorescence; Middle Aged; Risk Factors; Time Factors; Vitamin B 12

The question of whether mild hyperhomocysteinemia is a risk factor for coronary artery disease (CAD) has long been debated and is still unclear. We investigated whether there is a link between methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms or plasma homocysteine and CAD. This is a case-control study that included 2,121 consecutive patients (cases) with angiographically proved CAD and 617 patients without CAD (controls). MTHFR gene C677T and A1298C polymorphisms, plasma homocysteine, folate, and vitamin B(12) concentrations were determined and coronary angiography was performed in all subjects. The distribution of MTHFR gene C677T genotypes in patients (or controls) was: CC-genotype in 915 cases, 43.1% (266 controls, 43.1%); CT-genotype in 955 cases, 45.0%, (283 controls, 45.9%); and TT-genotype in 251 cases, 11.9% (68 controls, 11.0%) (p = 0.84). The distribution of MTHFR gene A1298C genotypes in patients (or controls) was: AA-genotype in 973 cases, 45.9% (281 controls, 45.5%); AC-genotype in 905 cases, 42.7% (284 controls, 46.0%); and CC-genotype in 243 cases, 11.4% (52 controls, 8.5%) (p = 0.07). Patients with CAD had higher levels of plasma homocysteine (12.9 +/- 5.1 vs 11.9 +/- 4.5 micromol/L, p <0.001) and lower levels of folate (9.5 +/- 3.1 vs 9.9 +/- 3.8 ng/ml, p = 0.008) than controls. After adjustment for other risk factors for CAD, plasma homocysteine (p = 0.89), MTHFR gene C677T (p = 0.38), or A1298C polymorphisms (p = 0.13) were not independent correlates of CAD. This study demonstrated that MTHFR gene C677T or A1298C polymorphisms are not associated with the presence of angiographic CAD. Although there is an apparent association between elevated levels of homocysteine and CAD, this association is not independent of conventional cardiovascular risk factors.

Topics: Aged; Biomarkers; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; DNA Primers; Female; Folic Acid; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymerase Chain Reaction; Polymorphism, Genetic; Severity of Illness Index; Vitamin B 12

Hyperhomocysteinemia is one of the newly recognised risk factors of coronary artery disease (CAD). The role of hyperhomocysteinemia in the development of atherosclerosis has been controversial.. To assess homocysteine (Hcy) plasma concentration in patients with CAD and to correlate Hcy level with some cardiovascular risk factors.. The study group consisted of 150 males aged <55 years (mean age 49.5+/-5.7 years) with stable CAD. Lipid and carbohydrate profiles as well as Hcy, folic acid and vitamin B(12) serum concentration were assessed, and correlated with such cardiovascular risk factors as cigarette smoking, hypertension, obesity and a history of myocardial infarction.. Mean Hcy plasma concentration was 11.81+/-3.75 micro mol/L. In patients with Hcy >11.21 micro mol/L (median value) a lower level of folic acid and vitamin B12 as well as reduced ejection fraction and glomerular filtration rate were found when compared to patients with Hcy level <11.21 micro mol/L. In addition, creatinine concentration, mean patient's age, proportion of patients who smoked cigarettes and the number of affected coronary arteries were significantly higher in patients with an increased level of Hcy. The Hcy plasma concentration positively correlated with the progression of hypertension, creatinine level and the number of coronary vessels with stenosis. A significant negative correlation between Hcy and folic acid as well as vitamin B12 concentrations was documented. In patients with a three-vessel CAD, Hcy concentration was 12.46+/-3.85 micro mol/L and was significantly higher (p<0.03) compared with patients with a less advanced CAD. In the group of patients with diabetes the mean Hcy concentration increased with the number of affected coronary vessels (p<0.02) and reached the highest values in patients with a three-vessel CAD (15.38+/-7.28 micro mol/L).. There is a significant relationship between homocysteine plasma concentration and the incidence as well as progression of CAD. This association is particularly evident in patients with diabetes.

Topics: Adult; Blood Glucose; Coronary Artery Disease; Disease Progression; Folic Acid; Homocysteine; Humans; Hypertension; Lipids; Male; Middle Aged; Myocardial Infarction; Obesity; Research Design; Risk Factors; Smoking; Vitamin B 12

This study aimed to assess whether folic acid supplementation could produce longer-term (6-month) improvements in homocysteine levels and arterial endothelial function in patients with a high risk (3 or more traditional risk factors) of coronary artery disease (CAD) and hyperhomocysteinaemia.. Thirty-one adults with 3 or more traditional risk factors of CAD and hyperhomocysteinaemia were selected, without CAD (the criterion of CAD is that more than one main vessel has an obstruction > or = 50%) by coronary angiography. All subjects were given folic acid (5 mg/day) for 6 months. Fasting plasma homocysteine levels were measured by high-performance liquid chromatography. Plasma folic acid and vitamin B12 levels were measured with immunoassay. Arterial endothelial function was measured as flow-mediated dilation of the brachial artery using high-resolution B-mode ultrasound.. Folic acid supplementation for 6 months was associated with a significant increase in mean (+/- SD) plasma levels of folic acid (4.6 +/- 1.4 microg/l to 9.1 +/- 2.5 microg/l; P < 0.01) and a significant decline in homocysteine levels (18.3 +/- 3.9 micromol/l to 11.5 +/- 2.8 micromol/l; P < 0.01). Flow-mediated dilation also improved significantly, from 6.8% +/- 2.1% to 8.9% +/- 1.7% (P < 0.01).. These results demonstrate that long-term (6-month) folic acid administration significantly declines homocysteine levels and improves arterial endothelial function and has potential implications for the prevention of atherosclerosis in adults with 3 or more traditional risk factors of CAD and hyperhomocysteinaemia.

Topics: Aged; Arteries; Chromatography, High Pressure Liquid; Coronary Artery Disease; Dietary Supplements; Endothelium, Vascular; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Risk Factors; Time; Treatment Outcome; Vitamin B 12

Hyperhomocysteinemia is a risk factor for vascular disease and potentially for dementia and depression. The most common cause of elevated homocysteine levels is deficiency of folate or vitamin B(12). However, patients with Parkinson disease (PD) may have elevated homocysteine levels resulting from methylation of levodopa and dopamine by catechol O-methyltransferase, an enzyme that uses S-adenosylmethionine as a methyl donor and yields S-adenosylhomocysteine. Since S-adenosylhomocysteine is rapidly converted to homocysteine, levodopa therapy may put patients at increased risk for vascular disease by raising homocysteine levels.. To determine whether elevations in plasma homocysteine levels caused by levodopa use are associated with increased prevalence of coronary artery disease (CAD), and to determine what role folate and vitamin B(12) have in levodopa-induced hyperhomocysteinemia.. Subjects included 235 patients with PD followed up in a movement disorders clinic. Of these, 201 had been treated with levodopa, and 34 had not. Blood samples were collected for the measurement of homocysteine, folate, cobalamin, and methylmalonic acid levels. A history of CAD (prior myocardial infarctions, coronary artery bypass grafting, or coronary angioplasty procedures) was prospectively elicited. We analyzed parametric data by means of 1-way analysis of variance or the t test, and categorical data by means of the Fisher exact test or chi(2) test.. Mean +/- SD plasma homocysteine levels were significantly higher in patients treated with levodopa (16.1 +/- 6.2 micro mol/L), compared with levodopa-naïve patients (12.2 +/- 4.2 micro mol/L; P<.001). We found no difference in the plasma concentration of folate, cobalamin, or methylmalonic acid between the 2 groups. Patients whose homocysteine levels were in the higher quartile (>or=17.7 micro mol/L) had increased prevalence of CAD (relative risk, 1.75; 95% confidence interval, 1.08-2.70;P=.04).. Levodopa therapy, rather than PD, is a cause of hyperhomocysteinemia in patients with PD. Deficiency of folate or vitamin B(12) levels does not explain the elevated homocysteine levels in these patients. To our knowledge, this is the first report that levodopa-related hyperhomocysteinemia is associated with increased risk for CAD. These findings have implications for the treatment of PD in patients at risk for vascular disease, and potentially for those at risk for dementia and depression.

Topics: Aged; Aged, 80 and over; Antiparkinson Agents; Coronary Artery Disease; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Levodopa; Male; Middle Aged; Parkinson Disease; Risk Factors; Vitamin B 12

To compare fasting serum total homocysteine (tHcy) concentrations in a randomly selected sample of elderly (> or = 65 years of age) Hispanic and non-Hispanic White (NHW) men and women, to examine associations of tHcy with folate and vitamin B12, and then to correlate these with the prevalence of coronary heart disease (CHD) in these 4 ethnic/ gender groups.. Equal numbers of Hispanic and NHW men and women were randomly selected from the Healthcare Financing Administration (Medicare) registrant list for Bernalillo County (Albuquerque), New Mexico, and asked to volunteer for a paid home interview, to be followed by a paid, comprehensive interview/examination covering health and health-related issues.. Serum concentrations of tHcy, folate, and vitamin B12 were determined and correlated with the prevalence of CHD, after adjusting for other CHD risk factors (age, diabetes, hypertension, smoking, dyslipidemia, adiposity).. Men and Hispanics had higher serum tHcy concentrations compared to women and non-Hispanic Whites (NHWs), respectively. After adjusting for lower concentrations of serum folate and vitamin B12 in Hispanics, the differences between Hispanics and NHWs were no longer significant. There was a direct association between serum tHcy concentrations and the prevalence of CHD after adjusting for other known risk factors that was most significant in Hispanic women.. The higher serum tHcy concentrations observed in Hispanics compared to NHWs can be explained by lower levels of serum folate and vitamin B12. A direct association between serum tHcy concentrations and prevalence of CHD was observed primarily in women, and was most significant in Hispanic women.

Topics: Aged; Coronary Artery Disease; Female; Folic Acid; Hispanic or Latino; Homocysteine; Humans; Male; New Mexico; Prospective Studies; Risk Factors; Urban Health; Vitamin B 12; White People

The C677T mutation in methylenetetrahydrofolate reductase (MTHFR) gene is one of the causes of an elevated homocysteine plasma concentration and is probably one of the atherosclerotic risk factors.. To assess the relationship between the presence of the MTHFR gene mutation, plasma homocysteine concentration and the risk of coronary artery disease (CAD).. The study group consisted of 120 consecutive patients (78% were male, mean age 59.2+/-9.6 years) with angiographically confirmed CAD and 106 healthy volunteers (76% were male, mean age 47.4+ or -6.0 years). The MTHFR gene mutation was detected based on the polymerase chain reaction and digestion with restrictive endonuclease HinfI. Total homocysteine plasma concentration was measured using HPLC. Folic acid and vitamin B12 plasma levels were assessed using the chemiluminescence method. Hyperhomocysteinemia was defined as homocysteine concentration > or =90 percentile of the control group which was > or =12.4 micro mol/L.. The incidence of the mutation of allele T and the genotype TT was similar in patients and controls (51.7% vs 56.6%, and 9.2% vs 10.4%, NS, respectively). The folic acid and vitamin B12 levels were not related to the MTHFR genotype (folic acid: 8.1 ng/L in homozygotes TT vs 8.6 in heterozygotes CT and 8.3 in homozygotes CC; and vitamin B12: 273 pg/L vs 303.3 vs 314.3, respectively). Although homozygotes TT had significantly higher homocysteine concentration than heterozygotes and homozygotes CT or CC (15.4 vs 11.0 vs 11.2 micro mol/L, p<0.001), the odds ratio for CAD in genotype TT was 0.87 (95% CI 0.5-2.1, NS). The odds ratio in subjects with at least one mutated T allele was 0.82 (95%CI 0.5-1.4, NS). Homocysteine plasma concentration was significantly higher in patients with CAD than controls (12.8+/-5.1 vs 10.0+/-5.0 micro mol/L, p<0.001) and correlated significantly with folic acid (r= -0.28, p=0.0001), vitamin B12 (r= -0.19, p<0.005), age (r=0.35, p=0.0001) and creatinine (r=0.26, p=0.0001). The odds ratio for CAD in subjects with hyperhomocysteinemia was 7.1 (95%CI 3.4-14.9, p=0.001) and was 2.6 (95%CI 1.6-4.1, p=0.0001) with a homocysteine increase of 5 micro mol/L. Multivariate analysis showed that hyperhomocysteinemia was an independent risk factor of CAD (OR 2.7, 95%CI 1-7.2, p<0.05). Conclusions. Hyperhomocysteinemia rather than a mutation in the methylenetetrahydrofolate reductase gene, is an independent risk factor of coronary artery disease.

Topics: Adult; Aged; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Cysteine; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Multivariate Analysis; Point Mutation; Polymerase Chain Reaction; Polymorphism, Genetic; Risk Factors; Threonine; Vitamin B 12

We investigated the influence of elevated homocysteine plasma levels and 2 polymorphisms, 677C/T and 1298A/C, of the methylenetetrahydrofolate reductase (MTHFR) gene on the risk of restenosis after stenting in patients with symptomatic coronary artery disease.. Homocysteine levels and MTHFR genotypes were determined in 800 consecutive patients treated with coronary artery stenting. Angiographic restenosis (> or =50% diameter stenosis at 6-month follow-up) was present in 25.8% of the patients with low homocysteine levels (at or below the median of 11.6 micromol/L; n=400) and 24.1% of the patients with high homocysteine levels (>11.6 micromol/L; n=400; P=0.62). Rates of angiographic restenosis were 26.0%, 23.5%, and 26.9% in carriers of the 677CC, 677CT, and 677TT genotypes (P=0.75), respectively, and 24.4%, 25.9%, and 24.0% in patients with the 1298AA, 1298AC, and 1298CC genotypes (P=0.90), respectively. The need for restenosis-driven reintervention (clinical restenosis) was 18.8% in subjects with low homocysteine concentrations and 19.0% in subjects with high homocysteine concentrations during the first year after the intervention (P=0.93). Rates of clinical restenosis were 19.5%, 17.1%, and 23.3% in carriers of the 677CC, 677CT, and 677TT genotypes (P=0.37), respectively, and 17.6%, 18.6%, and 24.7% in patients with the 1298AA, 1298AC, and 1298CC genotypes (P=0.27), respectively.. Elevated levels of homocysteine and 2 polymorphisms of the MTHFR gene are not associated with restenosis after stenting in coronary arteries.

Topics: Aged; Coronary Artery Disease; Coronary Restenosis; Female; Folic Acid; Follow-Up Studies; Genetic Predisposition to Disease; Genotype; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic; Postoperative Complications; Prosthesis Implantation; Stents; Thrombosis; Treatment Outcome; Vitamin B 12

Elevated levels of homocysteine is a risk factor for coronary artery disease. Polymorphic alleles in the MTHFR genes that cause recessively inherited increased homocysteine level can explain only a small proportion of the observed variation in homocysteine level. To investigate additional genetic influences, we examined environmental, familial, and genetic influences on serum homocysteine levels in 661 family members of 112 probands who underwent elective coronary arteriography. Maximum likelihood methods were used to fit several genetic and non-genetic models of inheritance to these data to determine if an unobserved Mendelian major gene could explain the familial homocysteine distribution. Adjustments for age, lifestyle (smoking and alcohol consumption), serum folate and vitamin B12, and the measured genotype effect of the MTHFR C677T mutation was carried out separately for males and females using multiple regression models for homocysteine, before and after log-transformation prior to this segregation analysis. After excluding the effects of mutations in the MTHFR genes, we found evidence of a major gene acting in a co-dominant manner. Estimated mean homocysteine levels for the three putative genotypes (LL, LH, and HH) were 8.0, 10.1, and 15.9 micro mol/l, respectively, with relative frequencies of 56.8%, 37.2%, and 6%, respectively. Our analysis suggested the presence of a co-dominantly expressed major gene, in addition to the effects of the MTHFR C677T mutation. The results of this study also indicated that multifactorial inheritance was supported more strongly than Mendelian inheritance alone. Our findings may have implications for attempts to identify new homocysteine susceptible genes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Chromosome Segregation; Coronary Angiography; Coronary Artery Disease; Family; Female; Folic Acid; Genotype; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Oxidoreductases Acting on CH-NH Group Donors; Pedigree; Vitamin B 12

The aim of this study was to investigate the known risk factors, such as lipids, homocysteine and endothelin, for the development of coronary artery disease (CAD) in phenylketonuria (PKU) patients, depending on their diet. The PKU patients (n = 74) were divided into two groups. Group A (n = 34; mean age 6.78 +/- 1.5 y) adhered strictly to a diet and group B (n = 40; mean age 8.0 +/- 3.2 y) did not comply with the diet. The control group comprised 50 healthy non-PKU children. All groups were evaluated for blood levels of homocysteine and vitamin B6 by high-performance liquid chromatography, vitamin B12 and folate in serum by a radioassay, lipids by a routine method, and lipoprotein(a) and endothelin-1 with an immunoassay. Homocysteine levels (28.65 +/- 3.3 micromol l(-1)) were increased in group A compared with group B (6.86 +/- 1.6 micromol l(-1)) and the controls (6.9 +/- 2.0 micromol l(-1)) (p < 0.001). Vitamin B6 (10.7 +/- 10.9 nmol l(-1)), vitamin B12 (98.5 +/- 22.3 pmol l(-1)), folate (2.35 +/- 1.3 nmol l(-1)) and lipids were decreased in group A. The other vascular risk factors, which were not dependent on diet [lipoprotein(a) and endothelin-1], did not differ among the three groups.. PKU patients on a strict diet had low vitamin B6, vitamin B12 and folate levels resulting in moderate hyperhomocysteinaemia. The evaluation of these vitamins at short intervals and their supplementation could be an early measure in the prevention of CAD.

Topics: Child; Child, Preschool; Coronary Artery Disease; Diet, Protein-Restricted; Endothelin-1; Folic Acid; Homocysteine; Humans; Lipids; Nutrition Assessment; Phenylalanine; Phenylketonurias; Risk Factors; Vitamin B 12; Vitamin B 6

The aim of this study was to test the hypothesis that chronic atrophic gastritis induced by Helicobacter pylori (H. pylori) causes malabsorption of vitamin B12 and folate in food, leading ultimately to an increase in circulating homocysteine levels.. We performed endoscopy with stomach biopsy and measured fasting plasma homocysteine, vitamin B12, and folate levels in 93 patients who underwent diagnostic coronary arteriography. The patients were divided into two groups according to the presence (n = 57) or absence (n = 36) of H. pylori infection. Positive H. pylori infection was defined as positive H. pylori histology of biopsy specimens from the stomach. The extent of atrophic gastritis was endoscopically graded from 0 to 6.. There were no differences in age, sex, or traditional coronary risk factors between the two groups. Atrophy scores of the stomach were greater in patients with H. pylori infection than in patients without (3.9 +/- 1.4 vs 2.2 +/- 1.8, p < 0.0001). Patients with H. pylori infection had lower levels of vitamin B12 (630 +/- 222 vs 747 +/- 259 pg/ml, p = 0.02) and folate (6.2 +/- 2.1 vs 7.4 +/- 2.8, p = 0.046), as well as higher levels of homocysteine (11 +/- 4.9 vs 8.3 +/- 2.1 nmol/ml, p = 0.01), than did patients without H. pylori infection. Plasma homocysteine levels correlated inversely with plasma vitamin B12 and folate levels and positively with atrophic scores.. This study suggests that H. pylori-induced chronic atrophic gastritis decreases plasma vitamin B12 and folic acid levels, thereby increasing homocysteine levels. However, this effect does not seem to be strong.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Female; Folic Acid; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Homocysteine; Humans; Malabsorption Syndromes; Male; Middle Aged; 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

The relationship between hyperhomocysteinemia and coronary artery disease (CAD) was investigated and the influence of environmental factors (Folate, VitB12) and genetic factors [N5, N10-methylenetetrahydrofolate reductase gene (MTHFR) or MTHFR gene mutation] on plasma homocysteine (Hcy) levels and the risk of CAD observed. Fifty-one CAD patients and 30 CAD-free subjects were recruited in the study. The polymorphisms of MTHFR gene were analyzed by PCR-RFLP and plasma total Hcy levels were measured by high performance liquid chromatography with fluorescence detection. Plasma folate and vitamin B12 concentrations were measured by an automated chemiluminescence method. It was found that mean total plasma Hcy concentrations were significantly higher in CAD patients than in CAD-free subjects (P < 0.01). The differences were also apparent among the three genotypes of MTHFR gene in CAD group (P < 0.05). There was no significant difference in the genotype distributions and allele frequencies between the two groups. A strong inverse correlation was found between folate or vitamin B12 and plasma Hcy levels according to MTHFR genotype (P < 0.01). It was concluded that hyperhomocysteinemia is a new independent risk factor for CAD. However, MTHFR gene mutation alone does not relate significantly to the morbidity of CAD since hyperhomocysteinemia and its influence on the risk of CAD are decided by both environmental and genetic factors. Supplementary treatment with vitamins B can effectively lower the plasma levels of Hcy, thus maybe reducing the risk of CAD.

Topics: Aged; Coronary Artery Disease; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Point Mutation; Polymorphism, Restriction Fragment Length; Vitamin B 12

Low folate levels are related to increased risk for coronary artery disease in humans, while experimental work has shown that folate deficiency is thrombogenic. We hypothesized that relatively low folate levels are related to the development of acute coronary syndromes in patients with previously stable coronary artery disease.. One hundred and forty-one men were studied: 53 consecutive patients with acute coronary syndromes, 41 with stable coronary artery disease and 47 control participants. Known clinical and lipid risk factors were identified in all subjects and in addition plasma B12, plasma and red cell folate levels were measured.. Red cell folate levels were significantly lower in patients with acute coronary syndromes (510+/-178 nmol/l) than in both stable coronary artery disease patients (638+/-264 nmol/l, P< 0.005) and controls (615+/-193 nmol/l, P< 0.05 respectively). Plasma folate and B12 levels were similar in all three groups. Multiple logistic regression analysis identified red cell folate levels as the only independent predictor of acute coronary events in the whole population of patients with known coronary artery disease and in the subgroup of non-smokers (P=0.010 and P=0.031).. The present study suggests that relatively low red cell folate levels are associated with acute coronary syndromes and are an independent predictor of acute coronary events.

Topics: Acute Disease; Cholesterol, HDL; Coronary Artery Disease; Erythrocytes; Folic Acid; Humans; Male; Predictive Value of Tests; Regression Analysis; Smoking; Syndrome; Vitamin B 12

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

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

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

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

To investigate the association of status of vitamins B6, B12 and folate with plasma fasting total homocysteine (tHcy) and with risk of coronary atherosclerosis; and to establish whether associations between vitamins and risk of coronary atherosclerosis are mediated by tHcy.. The study population consisted of 131 patients with angiography-defined severe coronary atherosclerosis and 88 referents with no or minor coronary stenosis. Previous analyses in this study population have shown that fasting tHcy is an independent risk factor for coronary atherosclerosis. In the present analyses, using multiple linear regression, we estimated differences in tHcy concentrations between subjects in the lowest and highest quartiles of concentrations of each of the vitamins, adjusting for age, gender, total:HDL cholesterol ratio, smoking habits, alcohol intake, blood pressure, serum creatinine, body mass index and the two other vitamins. We used logistic regression analysis conditional on the set of potential confounders described above to study the association between vitamin concentration and risk of coronary atherosclerosis. By comparing these estimated odds ratios (ORs) with those that were additionally adjusted for fasting tHcy, we determined whether the vitamins exerted their effects on disease risk via homocysteine metabolism.. Cases who were in the upper quartile of serum vitamin B12 and erythrocyte folate concentrations showed statistically significantly lower tHcy concentrations (-4.00 and -4.71 mumol/L, respectively) than those in the lowest quartile. Referents in the upper quartile of plasma B6 showed significantly lower tHcy concentrations (-2.36 mumol/L) than referents in the lowest quartile. Subjects in the lowest quartile of vitamin B12 concentrations had higher risk of coronary atherosclerosis (OR: 2.91; 95% CI: 1.10, 7.71) compared to those in the highest quartile. The ORs and 95% CIs for low B6 and low folate were 0.86 (95% CI: 0.33, 2.22) and 0.58 (95% CI: 0.23, 1.48), respectively. Additional adjustment for fasting tHcy weakened associations, although data indicated that low vitamin B12 concentration is a risk factor for coronary atherosclerosis, independently of tHcy.. The presently accepted view that vitamin B6 mainly affects tHcy after methionine loading, and not fasting tHcy, is contradicted by our findings in referents. Low vitamin B12 concentrations were associated with an increased risk of coronary atherosclerosis, partly independently of tHcy. Although low folate status was a strong determinant of elevated tHcy concentrations, it was not associated with increased risk of coronary atherosclerosis.

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

Epidemiological research has shown that elevated plasma total homocysteine (tHcy) is a risk factor for atherosclerotic disease. In the present case-control study, we investigated whether fasting or postmethionine-loading tHcy was a stronger predictor of risk of severe coronary atherosclerosis. Furthermore, we studied levels of B vitamins, which are involved in homocysteine metabolism. Subjects were recruited from men and women, aged 25 to 65 years, who underwent coronary angiography between June 1992 and June 1994 in a hospital in Rotterdam, The Netherlands. Cases (n=131) were defined as those with > or =90% occlusion in one and > or =40% occlusion in a second coronary artery, while control subjects (n=88) had <50% occlusion in only one coronary vessel. In addition, a population-based control group free from clinical cardiovascular disease (n=101) was studied. Coronary patients were studied at least 2.5 months after angiography or other acute illness, such as myocardial infarction. After adjusting for age and sex differences between the groups, cases had 9% (P=.01) higher geometric mean fasting and 7% (P=.04) higher geometric mean postload tHcy than the combined control groups. Despite higher levels of tHcy for cases, their geometric mean levels of red cell folate and pyridoxal 5'-phosphate were higher than for control subjects, whereas plasma vitamin B12 was only slightly lower in cases. The frequency distribution of tHcy values in cases was slightly shifted toward the right, across the entire range, compared with the distribution in the combined control group. This was somewhat more obvious for fasting than postload tHcy levels. The odds ratio (OR) for severe coronary atherosclerosis (case status) for each 1 SD increase in fasting tHcy (5 micromol/L) was 1.3 (95% confidence interval [CI], 1.0-1.6), similar to the OR for each 1 SD increase (12 micromol/L) in postmethionine-loading tHcy (1.3 [95 CI, 1.0-1.7]), after adjustment for sex, age, and other potential confounders. Furthermore, there was a significant linear trend of increasing fasting tHcy with increasing number of occluded arteries (P=.01), correcting for sex, age, and other potential confounders. Our data show a positive association between plasma tHcy and risk of severe coronary atherosclerosis, of similar strength for fasting and postload tHcy levels. The data suggest that the association exists over a wide range of tHcy levels, without a clear cutoff point below which there is no increased r

Topics: Adult; Aging; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Erythrocytes; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Pyridoxal Phosphate; Risk Factors; Sex Characteristics; Vitamin B 12; Vitamin B Complex

To examine the prevalence of hyperhomocysteinaemia and compare it with the classic risk factors and vitamin status in Hong Kong Chinese patients with premature atherosclerotic coronary artery disease.. Case-control study.. General hospital and community.. Forty five patients (39 males) with significant coronary artery disease confirmed by angiography (32 post myocardial infarction) and 23 healthy volunteers (17 male), all aged less than 55 years.. Standardised methionine-loading test.. Coronary artery disease, risk factors.. More patients than controls had fasting hyperhomocysteinaemia (10/45 v 2/23, P = 0.122), post-methionine hyperhomocysteinaemia (17/45 v 1/23, P = 0.008), and an abnormal response to methionine (15/45 v 1/23, P = 0.015). A history of smoking was more frequent in patients (3/23 v 25/45, P = 0.002). Sixteen of 17 patients with hyperhomocysteinaemia but only nine of 28 with normohomocysteinaemia were smokers (P = 0.0002). Fasting plasma cholesterol concentrations (mean (SD)) were higher in hyperhomocysteinaemic patients (6.41 (1.58) mmol/l) than in controls (5.53 (0.90) mmol/l) (P = 0.042). Serum vitamin B-12 was not reduced and serum folate was higher in hyperhomocysteinaemic patients (35 (4) nmol/l) than normohomocysteinaemic patients (26 (9) nmol/l) (P = 0.009).. Although the prevalence of hyperhomocysteinaemia in Hong Kong Chinese is similar to that in white subjects, hyperhomocysteinaemia is not an independent risk factor for coronary artery disease and is associated with smoking. This may be of some consequence in view of the change to a more Western diet with more animal protein, and therefore methionine, coupled with a high frequency of cigarette smokers in this region. The causes of the hyperhomocysteinaemia are multifactorial but in this pilot study a deficiency of folate and/or vitamin B-12 did not seem to be one of them.

Topics: Adult; Case-Control Studies; China; Cholesterol; Coronary Artery Disease; Female; Folic Acid; Homocysteine; Hong Kong; Humans; Male; Middle Aged; Prevalence; Risk Factors; Smoking; 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: Cardiotonic Agents; Coronary Artery Disease; Coronary Disease; Hematinics; Humans; Testosterone; Vitamin B 12; Vitamin B Complex

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