vitamin-b-12 and Peripheral-Vascular-Diseases

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

Hyperhomocyst(e)inemia is a risk factor for atherosclerotic vascular disease, and it is associated with endothelial dysfunction. Mechanisms responsible for endothelial dysfunction in hyperhomocyst(e)inemia may involve impaired bioavailability of NO, possibly secondary to accumulation of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) and increased oxidative stress. We investigated whether oral treatment with B vitamins or L-arginine normalizes endothelium-dependent, flow-dependent vasodilation (FDD) in patients with peripheral arterial occlusive disease (PAOD) and hyperhomocyst(e)inemia.. 27 patients with PAOD and hyperhomocyst(e)inemia were assigned to oral treatment with combined B vitamins (folate, 10 mg; vitamin B-12, 200 microg; vitamin B-6, 20 mg/day), L-arginine (24 g/day) or placebo, for 8 weeks in a double-blind fashion. FDD was determined by high-resolution ultrasound in the radial artery.. Vitamin B supplementation significantly lowered plasma homocyst(e)ine concentration from 15.8+/-1.8 to 8.7+/-1.1 micromol/l (P<0.01). However, B vitamins had no significant effect on FDD (baseline, 7.8+/-0.7%, B vitamins, 8.3+/-0.9%, placebo 8.9+/-0.7%; P=n.s.). In contrast, L-arginine treatment did not affect homocyst(e)ine levels, but significantly improved FDD (10.2+/-0.2%), probably by antagonizing the impact of elevated ADMA concentration (3.8+/-0.3 micromol/l) and reducing the oxidative stress by lowering urinary 8-iso-prostaglandin F(2alpha) (baseline, 76.3+/-7.1 vs. 62.7+/-8.3 pmol/mmol creatinine after 8 weeks).. Oral supplementation with combined B vitamins during 8 weeks does not improve endothelium-dependent vasodilation in PAOD patients with hyperhomocyst(e)inemia, whereas L-arginine significantly improved endothelial function in these patients. Thus, accumulation of ADMA and increased oxidative stress may underlie endothelial dysfunction under hyperhomocyst(e)inemic conditions. These findings may have importance for evaluation of homocyst(e)ine-lowering therapy.

Topics: Aged; Analysis of Variance; Arginine; Arterial Occlusive Diseases; Double-Blind Method; Female; Folic Acid; Humans; Hyperhomocysteinemia; Male; Middle Aged; Nitric Oxide Synthase; Oxidative Stress; Peripheral Vascular Diseases; Vitamin B 12; Vitamin B 6; Vitamins

Topics: Aged; Diagnosis, Differential; Female; Humans; Peripheral Vascular Diseases; Plasma; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Vitamin B 12; Vitamin B 12 Deficiency

Homocysteine is associated with age, folate and vitamin B(12). Our study investigated the functional and clinical characteristics of the elderly (aged 60-85 years) of San Teodoro, a village in Central Sicily, and evaluated associations with vitamin B(12), folate and homocysteine.. Subjects (n=280) were examined after door-to-door recruitment using interview, physician examination and laboratory tests.. A total of 19.3% of the population had a low blood level of folate (<7 nmol/L) and 3.2% had low vitamin B(12) concentration (<100 pmol/L). The level of dependency, determined by the Barthel index, influenced homocysteine blood levels (p<0.0001), independent of age (p<0.0001), folate (p=0.0028) and vitamin B(12) (p=0.0165). Homocysteine was significantly associated with stroke (p=0.0027) and peripheral arterial vascular disease (p=0.0001), but not with myocardial infarction, angina pectoris, venous thrombosis or cancer. Vitamin B(12) was lower in myocardial infarction and higher in diabetes and venous thrombosis compared to the other diseases.. The prevalence of deficits in folate and vitamin B(12) was paradoxically high in the mountainous northeastern area of Sicily. Our study also underlines the association of homocysteine with dependency of the elderly and with stroke and peripheral arteriopathy.

Topics: Aged; Aged, 80 and over; Aging; Cardiovascular Diseases; Diabetes Mellitus; Folic Acid; Homocysteine; Humans; Middle Aged; Neoplasms; Peripheral Vascular Diseases; Sicily; 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

Topics: Aged; Aortic Aneurysm, Abdominal; Atherosclerosis; Carotid Artery Diseases; Folic Acid; Genotype; Homocysteine; Humans; Ischemia; Leg; Male; Methylenetetrahydrofolate Reductase (NADPH2); Peripheral Vascular Diseases; Risk Factors; Vitamin B 12

It has been suggested that hyperhomocysteinemia (HHcy) is an independent risk factor for peripheral arterial occlusive disease (PAOD). However, the relationship between dietary folate and vitamin B6, cofactors in the metabolism of homocysteine (Hcy), and PAOD is unclear.. To study the relationship between dietary folate and B6 and PAOD.. Case-control population based study of 392 men older than 50 years living in Huntingdon, United Kingdom. PAOD, defined as an ankle-brachial pressure index (ABPI) < 0.9, was present in 86 (22%) of subjects. Folate, vitamin B6, and vitamin B12 intakes were calculated by means of the EPIC (European Prospective Investigation into Cancer) food frequency questionnaire.. Daily folate intake was significantly lower in case subjects (mean, 288; 95% confidence interval [CI], 266-309 microg) than in control subjects (324; 95% CI, 313-335 microg). Daily vitamin B6 intake was also lower in case subjects (2.05; 95% CI, 1.92-2.19 mg versus 2.26; 95% CI, 2.19-2.33 mg). Daily folate and vitamin B6 intakes were independent predictors of PAOD after adjusting for age, blood pressure, cholesterol levels, diabetes, and smoking status in a logistic regression model. This model suggests that increasing daily folate intake by 1 standard deviation decreased the risk of PAOD by 46%. A similar increase in daily vitamin B6 intake decreased the risk of PAOD by 29%.. In men older than 50 years, dietary folate and B6 intakes are independent predictors of PAOD. Longitudinal studies are required to determine whether dietary modification can reduce the incidence of PAOD in the population.

Topics: Aged; Aged, 80 and over; Arterial Occlusive Diseases; Cohort Studies; Diet; Diet Surveys; Folic Acid; Humans; Male; Middle Aged; Peripheral Vascular Diseases; Risk Factors; United Kingdom; Vitamin B 12; Vitamin B 6

A case-control study was undertaken involving 51 consecutive patients with peripheral artery obstructive disease (PAOD) scheduled for angioplasty. Blood samples of these patients were analysed for plasma homocysteine (tHcy) and levels of vitamin B12 and folate, and the MTHFR gene was assessed for mutation. Patients were compared with age- and sex-matched controls who did not present with cardiovascular risk factors. Mean tHcy did not differ between cases and controls (13.3 +/- 5.7 and 12.6 +/- 4.9 micromol/l, P = 0.49). More patients were above the 95th percentile as determined from the data in the control group with an odds ratio (OR) that almost reached statistical significance [OR, 2.8; 95% confidence interval (CI), 0.9-8.7], but on separate analyses only female patients showed higher tHcy than female controls (15.6 versus 12.0 micromol/l, P = 0.05), with an odds ratio for tHcy above the 95th percentile of 10.5 (95% CI, 1.1-96.6). The TT genotype of the MTHFR gene was found in 24% of the patients and in 12% of the controls (OR, 2.3; 95% CI, 0.8-6.7). Our findings point to a modest association between tHcy and PAOD, with a difference between cases and controls restricted to the highest percentile in female patients. A weak but not significant association was also found for the TT genotype of the MTHFR gene.

Topics: Adult; Aged; Arterial Occlusive Diseases; Case-Control Studies; Female; Folic Acid; Genotype; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Oxidoreductases Acting on CH-NH Group Donors; Peripheral Vascular Diseases; Vitamin B 12

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

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

Plasma homocysteine is a risk factor for peripheral arterial disease.. In a cross-sectional study design we investigated the association between plasma homocysteine, vitamin B12 and folate concentrations, and the prevalence of peripheral arterial disease in 158 men and 362 women, mean age 81 +/- 8 years.. Univariate analysis showed that plasma homocysteine, vitamin B12 (inverse association) and folate (inverse association) concentrations and increased plasma homocysteine and low or indeterminate vitamin B12 concentrations were risk factors for peripheral arterial disease in older men and women. Stepwise multiple logistic regression analysis showed that significant independent risk factors for peripheral arterial disease were a greater value of plasma homocysteine (P = 0.0001; odds ratio = 1.125) and a low value of plasma folate (P = 0.0001; odds ratio = 0.709).. High plasma concentrations of homocysteine and low plasma concentrations of folate are significant independent risk factors for peripheral arterial disease in older men and women.

Topics: Aged; Aged, 80 and over; Cross-Sectional Studies; Female; Folic Acid; Homocysteine; Humans; Logistic Models; Male; Peripheral Vascular Diseases; Prevalence; Risk Factors; Vitamin B 12

Topics: Corrinoids; Hematinics; Humans; Peripheral Vascular Diseases; Vascular Diseases; Vitamin B 12