Plasma Sulfur Amino Acids and Risk of Cerebrovascular Diseases: A Nested Case-Control Study in the EPIC-Norfolk Cohort.

BACKGROUND AND PURPOSE: B-vitamin supplements lower circulating concentrations of homocysteine and may reduce stroke incidence. Homocysteine concentrations are associated with the incidence of stroke but other sulfur-containing compounds in the related metabolic pathway have not yet been investigated for an association with incident cerebrovascular diseases. METHODS: Nested within the EPIC (European Prospective Investigation Into Cancer and Nutrition)-Norfolk cohort, we established a case-control study with 480 incident cases of cerebrovascular diseases and 480 controls matched by age, sex, and year of baseline examination (1993-1997). Using baseline plasma samples, we assayed sulfur-containing compounds including methionine, homocysteine, cystathionine, cysteine, glutathione, and taurine with liquid chromatography-tandem mass spectrometry. We examined the association of concentrations of each of the compounds and the ratio of methionine to homocysteine (representing activity of one-carbon metabolism) with risk of incident cerebrovascular diseases, adjusted for potential confounders. RESULTS: Plasma methionine and the methionine/homocysteine ratio were inversely associated with risk of cerebrovascular diseases, with odds ratios per 1 SD of 0.83 (95% CI, 0.72-0.96) and 0.82 (95% CI, 0.71-0.95), respectively. The association of methionine remained significant after adjustment for homocysteine. None of the other examined compounds was significantly associated with incident cerebrovascular diseases. CONCLUSIONS: These findings suggest that greater availability of methionine, an essential amino acid, may play a role in the prevention of cerebrovascular diseases and explain the previously recognized link between elevated homocysteine and stroke. Further research is needed to determine causation and the potential of circulating methionine as a target in cerebrovascular disease prevention.

Association between hyperhomocysteinemia and stroke with atherosclerosis and small artery occlusion depends on homocysteine metabolism-related vitamin levels in Chinese patients with normal renal function.

This study was conducted to investigate the role of different homocysteine metabolism-related vitamin (HMRV) levels in the correlation between hyperhomocysteinemia (HHCY) and ischemic stroke (IS) subtypes. Three hundred and forty-eight IS patients manifesting different vascular subtypes were subclassified on the basis of HMRV deficiencies. Correlation between HHCY and IS subtypes was investigated in all the subgroups. In this study, HHCY was significantly correlated with the IS subtypes in large artery atherosclerosis (OR 1.126, 95%CI: 1.051 ~ 1.206, P = 0.001) and small artery occlusion (OR 1.105, 95%CI: 1.023 ~ 1.193, P = 0.012). Subgroup analysis revealed a correlation between HHCY and IS subgroup (OR 1.201, 1.178, 95%CI: 1.081 ~ 1.334, 1.058 ~ 1.313, P = 0.001, P = 0.003, respectively) in HMRV deficiency, but not significantly with the IS subgroup in normal HMRV levels. Serum vitamin B12 concentrations are inversely correlated with both IS subtypes in HMRV deficiency subgroups (OR 0.992, 0.995, 95%CI: 0.987 ~ 0.996, 0.991 ~ 0.999, P < 0.001, P = 0.007, respectively), which may contribute to HHCY incidence in these populations. The correlation between HHCY and IS subtypes is affected by HMRV levels in this case-control study. Our findings are helpful to understand the inconsistency in prior homocysteine studies. Serum vitamin B12 levels may play a critical role in HHCY incidence in this Chinese population.Cerebrovascular disease has emerged as the leading cause of disability and mortality in both urban and rural areas of China (Neurology branch of Chinese Medical Association 2015). Ischemic stroke (IS) constitutes 60% to 80% of all cerebrovascular disease (Neurology branch of Chinese Medical Association 2014). Among a variety of risk factors, hyperhomocysteinemia (HHCY) has been closely correlated with IS due to intracranial small-vessel disease and extracranial large-artery disease (Selhub et al. 1995; Eikelboom et al. 2000; Alvarez et al. 2012; Jeon et al. 2014). However, the failure to lower homocysteine (HCY) via homocysteine metabolism-related vitamin (HMRV, including folic acid and vitamin B12 but not vitamin B6 in this study) supplementation to reduce stroke morbidity questions the role of HCY as a risk factor for stroke (Lonn et al. 2006; Hankey et al. 2010). Theoretically, HMRV supplementation merely lowers the incidence of stroke induced by HHCY resulting from HMRV deficiency, whereas HHCY-induced stroke concomitant with normal HMRV levels may be refractory to treatment. The correlation between HCY varying with HMRV levels and IS subtypes is still unclear. In this study, we investigated the impact of variation in HMRV levels on the correlation between HHCY and IS subtypes in 348 acute IS patients with large and small vessel diseases. We sought to determine the factors underlying the conflicting results associated with lowering HCY by HMRV supplementation to reduce stroke incidence.

High red blood cell folate is associated with an increased risk of death among adults with diabetes, a 15-year follow-up of a national cohort.

BACKGROUND AND AIM: To describe the mortality and fatality of diabetes and assess their relationship with the level of red blood cell (RBC) folate. METHODS AND RESULT: We analyzed the data of 526 adults with diabetes who participated in the National Health and Nutrition Examination Survey (1991-1994) as the baseline examination, and were followed up through December 31, 2006. Estimates of the hazard ratios (HRs) of selected death causes for individuals with different levels of RBC folate were obtained from Cox proportional hazards regression. A total of 295 deaths were recorded by the end of a 15-year follow-up with a mortality rate of 58.48 per 1000 person year (py). Diabetes was listed as a contributing cause for 136 deaths, accounting for 46.1% of the total deaths with a fatality rate 26.96 per 1000 py. Mortality rate for all-cause in the group with upper quartile of RBC folate was almost twice as high as that among the group with lower quartile, 82.75 vs. 44.10 per 1000 py. After adjusting for covariates, including serum concentration of vitamin B12, cotinine, homocysteine and the history of cardio-cerebral vascular diseases assessed at the baseline, the HRs for dying from any causes were 1.00 (reference), 1.82 (95% CI = 1.25-2.66) and 2.10 (1.37-3.20) among diabetic adults with lower, intermediate, and upper quartiles of RBC folate. CONCLUSION: Diabetes was listed as a contributing cause for less than half of the deaths among adults with diabetes after 15+ years of follow-up; high RBC folate concentration was associated with an elevated risk of death among adults with diabetes.

Homoarginine in the renal and cardiovascular systems.

Homoarginine (hArg) is an endogenous, nonproteinogenic amino acid which differs from arginine by an additional methylene (CH2) group in the backbone. In this brief narrative review, we summarize the current literature on hArg in the renal and cardiovascular systems. Epidemiological studies have identified low hArg levels as an independent risk marker for cardiovascular, cerebrovascular, and renal diseases as well as for mortality. The relatively low correlation of hArg with established cardiovascular risk factors underlines its great potential as an emerging biomarker to improve risk prediction because plasma hArg concentrations might reflect previously unrecognized pathophysiological processes. hArg may be involved in the pathogenesis of various diseases due to its effects on nitric oxide (NO) and energy metabolism. In view of its structural similarities with arginine, it has been proposed that hArg impacts on arginine metabolism and subsequently also on NO synthesis. The key enzyme for hArg synthesis, arginine:glycine amidinotransferase (AGAT), is involved in the synthesis of energy metabolites including guanidinoacetate, the precursor of creatine. Therefore, the involvement of hArg in energy metabolism could partially explain the close association between hArg and cardiovascular diseases such as heart failure. Whether hArg supplementation or modification of key enzymes of hArg metabolism such as AGAT activity is effective for the treatment of chronic diseases remains to be elucidated.

Vitamin D status and the risk of major adverse cardiac and cerebrovascular events in cardiac surgery.

AIMS: A significant proportion of cardiac surgical patients develop critical post-operative complications. We aimed to investigate the association of pre-operative 25-hydroxyvitamin D (25(OH)D) levels with major cardiac and cerebrovascular events (MACCE) in cardiac surgical patients. METHODS AND RESULTS: From January 2010 to August 2011, we consecutively measured circulating 25(OH)D in 4418 operated patients. Of the study cohort, 38.0% had deficient 25(OH)D values (<30 nmol/L) and additional 32.3% had insufficient values (30-49.9 nmol/L), whereas only 3.1% had values >100 nmol/L. The incidence of MACCE was 11.5%. In multivariable-adjusted logistic regression models, the odds ratio of MACCE at deficient, inadequate, and high 25(OH)D levels was 2.23 [95% confidence interval (CI): 1.31-3.79], 1.73 (95% CI: 1.01-2.96) and 2.34 (95% CI: 1.12-4.89), respectively, compared with 25(OH)D levels of 75-100 nmol/L. A U-shaped association with circulating 25(OH)D was also present for duration of mechanical ventilatory support and intensive care unit stay. Multivariable-adjusted 6- and 12-month mortality were higher in patients with deficient 25(OH)D levels compared with patients with 25(OH)D levels of 75-100 nmol/L. CONCLUSION: Deficient 25(OH)D levels are prevalent in cardiac surgical patients in Central Europe and are independently associated with the risk of MACCE. Further research should clarify the potential of vitamin D supplements in reducing cardiovascular risk in vitamin D-deficient patients and also the mechanisms leading to adverse effects on the cardiovascular system in the small group of patients with 25(OH)D levels >100 nmol/L.

[Rehabilitation of the patients presenting with combined pathology: dyscirculatory encephalopathy and climacteric syndrome].

The present paper reports the data on rehabilitation of women presenting with combined pathology: dyscirculatory encephalopathy and climacteric syndrome. It is shown that the introduction of ozonotherapy and klimadynon, a herbal medicine possessed of the estrogen-like action, into combined rehabilitative treatment ensures the significant improvement of the parameters of interest, such as climacteric symptoms, short-term memory, lipid profile, endothelial function, cerebral circulation, and quality of life.

Probucol prevents blood-brain barrier dysfunction in wild-type mice induced by saturated fat or cholesterol feeding.

Dysfunction of the blood-brain barrier (BBB) is an early pathological feature of vascular dementia and Alzheimer's disease (AD) and is triggered by inflammatory stimuli. Probucol is a lipid-lowering agent with potent anti-oxidant properties once commonly used for the treatment of cardiovascular disease. Probucol therapy was found to stabilize cognitive symptoms in elderly AD patients, whereas in amyloid transgenic mice probucol was shown to attenuate amyloidosis. However, the mechanisms underlying the effects of probucol have note been determined. In the present study we investigated whether probucol can prevent BBB disturbances induced by chronic ingestion of proinflammatory diets enriched with either 20% (w/w) saturated fats (SFA) or 1% (w/w) cholesterol. Mice were fed the diets for 12 weeks before they were killed and BBB integrity was measured. Mice maintained on either the SFA- or cholesterol-supplemented diets were found to have a 30- and sevenfold greater likelihood of BBB dysfunction, respectively, as determined by the parenchymal extravasation of plasma-derived immunoglobulins and endogenous lipoprotein enrichment with ß-amyloid. In contrast, mice fed the SFA- or cholesterol-enriched diets that also contained 1% (w/w) probucol showed no evidence of BBB disturbance. The parenchymal expression of glial fibrillary acidic protein, a marker of cerebrovascular inflammation, was significantly greater in mice fed the SFA-enriched diet. Plasma lipid, ß-amyloid and apolipoprotein B levels were not increased by feeding of the SFA- or cholesterol-enriched diets. However, mice fed the SFA- or cholesterol-enriched diets did exhibit increased plasma non-esterified fatty acid levels that were not reduced by probucol. The data suggest that probucol prevents disturbances of BBB induced by chronic ingestion of diets enriched in SFA or cholesterol by suppressing inflammatory pathways rather than by modulating plasma lipid homeostasis.

Serum calcium, phosphorus and cardiovascular events in post-menopausal women.

BACKGROUND: There is increasing evidence linking phosphorus and calcium levels to a higher risk of cardiovascular morbidity and mortality in the general population. METHODS: We performed a post hoc data analysis from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial of raloxifene treatment in 7259 postmenopausal women with osteoporosis to test the hypothesis that higher baseline calcium and phosphorus levels are associated with a higher risk of incident cardiovascular events during 4years of follow-up. RESULTS: Baseline mean (SD) values were 2.3 (0.1)mmol/L for serum calcium, 1.2 (0.2)mmol/L for serum phosphorus. Adjusted for multiple covariates including 25(OH)D, parathyroid hormone, and phosphorus, adjusted hazard ratios (AHR) (95% confidence interval (CI)) per SD of calcium were: 1.17(1.01-1.35), p=0.03 for combined cardiovascular outcome, 1.22(0.99-1.49), p=0.06 for cerebrovascular events, 1.12(0.92-1.37), p=0.25 for coronary heart disease, and 1.18(0.94-1.48), p=0.16 for death. While there was some evidence that higher serum phosphorus levels were associated with higher rate of combined cardiovascular outcome (p=0.07) and cerebrovascular events (p=0.03) in pauci-variable analysis, these associations did not persist after adjustment for additional confounders. Adjusted for multiple covariates including 25(OH)D, parathyroid hormone, and calcium, AHR(95% CI) per SD of phosphorus were 0.88(0.77-1.01), p=0.07 for combined cardiovascular outcome, 0.86(0.70-1.06), p=0.15 for ceverbrovascular events, 0.92(0.76-1.10), p=0.35 for coronary heart disease, and 1.00(0.80-1.25) for death. CONCLUSION: We found an independent association between higher baseline serum calcium levels and higher rate of cardiovascular events. Our findings did not support an independent association between serum phosphorus levels and cardiovascular events.

The effect of folinic acid supplementation on homocysteine concentrations in newborns.

OBJECTIVE: The incidence of cerebrovascular accidents (CVA) occurring perinatally is relatively high and aspects of the multifactorial pathophysiology remain unclear. Elevated homocysteine concentrations have been shown to be associated with an increased risk for CVA in children and even in newborns. We studied the possible homocysteine lowering effect of folinic acid in newborns. METHOD: We included 37 newborns in our prospective randomized folinic acid (given as 5-formyltetrahydrofolate) intervention study from patients admitted to our neonatal intensive care unit (18 controls, 19 intervention group). We measured total homocysteine (tHcy) and plasma folate concentrations at three time points (baseline, 1 and 2 weeks after intervention). The intervention group was treated with folinic acid (70 µg/kg/day) for 2 weeks. We calculated median concentrations (25th and 75th percentiles). RESULTS: Median tHcy concentrations at the three time points did not differ from each other in the control group nor in the intervention group. We also could not observe different tHcy concentrations between both groups. Plasma folate concentrations increased in the intervention group (mean increase 167% (95% confidence interval (CI) -291, 625)) compared with control group (mean increase -12% (95% CI -132, 108)), P for treatment effect: 0.03. CONCLUSION: We could not demonstrate a homocysteine lowering effect of folinic acid administration in newborns. This indicates that one carbon metabolism in newborns differs form adults. Cobalamin might be a better strategy to lower tHcy concentrations in newborns.

[Vitamin treatments that lower homocysteine concentration: can they decrease cerebrovascular disease in primary prevention?]. / Tratamientos vitaminicos para disminuir la concentracion de homocisteina: reducen el riesgo de enfermedad cerebrovascular en prevencion primaria?

INTRODUCTION: High plasma homocysteine (Hcy) concentration or hyperhomocysteinemia is associated with an increased vascular risk of disease in case-control studies and, to a lesser extent, in prospective studies. DEVELOPMENT: Several large randomized, double-blind, placebo-controlled trials have been already conducted using specific vitamin therapies with the aim of reducing secondary cardiovascular (HOPE, NORVIT, WAFACS and WENBIT studies) and cerebrovascular (VISP study) disease risk. The results from these major secondary prevention trials and one meta-analysis, that included other smaller studies up to 12 of them, showed that treatment decreased plasma Hcy concentration but failed to reduce cardiovascular risk. It is nevertheless noteworthy that a recent meta-analysis addressing the effects of these vitamin treatments on cerebrovascular risk found a positive effect on primary stroke prevention. These data would be consistent with the fact that increased Hcy is known to be associated more strongly with stroke risk than with cardiovascular risk. Moreover, folic acid supplementation in grain food has recently been shown to be associated with a decreased stroke incidence in USA and Canada. CONCLUSIONS: Obviously, these data on primary stroke prevention will require extensive confirmation. However, there now appear to be more reasons to expect a positive outcome of Hcy intervention studies.

[Removing phlegm and dispelling stasis method combined with Western medicine for treatment of cerebrovascular stenosis].

OBJECTIVE: To investigate the effect of removing phlegm and dispelling stasis method (RPDSM) combined with Western medicine for treatment of cerebrovascular stenosis. METHODS: Seventy enrolled patients were randomly assigned to 3 groups: the Western medicine (WM) group, the integrative medicine (IM) group, and the traditional Chinese medicine (TCM) group. The 21 patients in the WM group were treated with Western medicine as aspirin, Clopidogrel, statins, etc.; the 23 patients in the TCM group were treated with Chinese drugs using the patent preparation Dahuang Zhechong Pill and Tianma Duzhong Capsule as the basic drugs, and supplemented by self-formulated decoctions, selected according to their syndrome types (Tanshi Recipe for dampness-phlegm syndrome, Tanhuo Recipe for fire-phlegm syndrome, Qixu Recipe for qi-deficiency syndrome, and Yang-kang Recipe for yang-excess syndrome); and the 26 patients in the IM group were treated by both TCM and WM with the same drugs and doses mentioned above. The course of treatment was 3 months, and all patients received at least 2 courses in succession. Changes in clinical symptoms and TCM syndrome, levels of C-reactive protein (CRP), platelet aggregation rate (PAR) and fibrinogen (Fib), as well as pictures of medical imaging were observed to evaluate cerebrovascular stenosis. RESULTS: After 6-month treatment, the blood levels of CRP, PAR and Fib were lowered and the number of moderate and severe stenosed vessel lessened in all the three groups (all P < 0.05). The respective total effective rate in the WM, TCM and IM group was 42.9% (9/21 cases), 39.1% (9/23 cases) and 61.5% (16/26 cases), no significant difference was shown among them. CONCLUSION: The integrative Chinese traditional and Western medical treatment for cerebrovascular stenosis shows an increasing trend in improving clinical efficacy and laboratory indexes, combared with pure Western or Chinese medical treatment.

Effects of high-dose atorvastatin on cerebrovascular events in patients with stable coronary disease in the TNT (treating to new targets) study.

OBJECTIVE: We sought to assess the effects on cerebrovascular events of treating patients with stable coronary disease with low-density lipoprotein cholesterol (LDL-C) levels substantially below 100 mg/dl. BACKGROUND: Lowering LDL-C with statins has been shown to reduce the risk of stroke in patients with stable coronary disease. In observational studies, naturally low cholesterol levels have been associated with an increased risk of hemorrhagic stroke. The cerebrovascular benefits of treating patients with stable coronary disease to LDL-C levels substantially below 100 mg/dl have not been previously investigated. METHODS: We describe an analysis of cerebrovascular events in the Treating to New Targets study, a trial where 10,001 patients with documented coronary disease were randomized to treatment with atorvastatin at 10 mg/day or 80 mg/day and followed for a median of 4.9 years. RESULTS: Mean LDL-C levels were 101 mg/dl on 10 mg atorvastatin and 77 mg/dl on 80 mg. In addition to the reduction in major cardiovascular events (hazard ratio 0.78, 95% confidence interval [CI] 0.69 to 0.89; p = 0.0002), the primary end point of the trial, patients in the 80-mg arm experienced a reduction in cerebrovascular events (hazard ratio 0.77, 95% CI 0.64 to 0.93; p = 0.007) and stroke (hazard ratio 0.75, 95% CI 0.59 to 0.96; p = 0.02). Each 1-mg/dl reduction in LDL-C with treatment was associated with a 0.6% relative risk reduction in cerebrovascular events (p = 0.002) and a 0.5% relative risk reduction in stroke (p = 0.041). The incidence of hemorrhagic stroke was similar in the 80-mg and 10-mg groups, 16 and 18 respectively, and the hemorrhagic strokes were distributed evenly across quintiles of achieved LDL-C during treatment. CONCLUSIONS: Among patients with established coronary disease, treating to an LDL-cholesterol substantially below 100 mg/dl with 80 mg/day atorvastatin reduces both stroke and cerebrovascular events by an additional 20% to 25% compared with the 10 mg/day dose. An increase in hemorrhagic stroke was not seen at low LDL-C levels. (Treating to New Targets; http://www.clinicaltrials.gov; NCT00327691).

Increase in plasma homocysteine levels induced by drug treatments in neurologic patients.

Homocysteine (Hcy) is a thyol amino acid resulting from de-methylation of methionine, an essential amino acid derived from dietary proteins. It is metabolized through two pathways: re-methylation and transsulfuration, which use as cofactors folate, vitamin B6 and vitamin B12. Hyperhomocysteinemia has been identified as a risk factor for cerebrovascular disease, dementia, impaired cognitive function and depression. Several drugs may interfere with metabolic pathways of Hcy, leading to an alteration of plasma Hcy levels. Lipid-lowering agents, used to reduce the risk of cerebral venous thrombosis or occlusive vascular disease in patients with high levels of plasmatic lipids, can increase plasma Hcy levels. Hyperhomocysteinemia has been also documented in Parkinson disease patients treated with levodopa and in epileptic patients after chronic treatment with antiepileptic drugs. In contrast, vitamins supplementations may be warranted in patients treated with lipid-lowering agents, levodopa and antiepileptic drugs in order to maintain normal plasma Hcy values. In contrast, higher doses of vitamins can induce dysfunctions in central and peripheral nervous system; therefore excessive supplements should be avoided.

[Hypokalemia can accelerate the development of cerebrovascular and cardiovascular disease]. / Hypokalemi kan påskynde utviklingen av cerebro- og kardiovaskulaer sykdom.

BACKGROUND: Hypokalaemia is known to precipitate cardiac arrhythmias. Hypokalaemia can also give rise to adverse cardiovascular effects not related to arrhythmias. MATERIAL AND METHODS: This article presents an evaluation of the relevant literature describing adverse effects of hypokalaemia and beneficial effects of potassium supplementation on cerebrovascular and cardiovascular disease. RESULTS AND INTERPRETATION: Diuretics-induced hypokalaemia may offset the beneficial effects of blood pressure reduction on cardiovascular events. In several epidemiological studies high intake of potassium in the food was associated with reduced risk of developing a stroke. Fruit and vegetables contain potassium, and an inverse correlation between intake of these nutrients and stroke has been described. In spontaneously hypertensive rats, potassium supplementation in the diet markedly reduced the risk of death, brain haemorrhage and infarct. Potassium reduces oxidative stress and proliferation of smooth muscle cells, i.e. factors involved in the development of atherosclerosis, and may have an antithrombotic effect.

[Study of molecular damage in bronchial asthma and cerebrovascular disorders during the course of rehabilitation ]. / Izuchenie molekuliarnykh povrezhdenii pri bronkhial'noi astme i tserebrovaskuliarnykh narusheniiakh v protsesse vosstanovitel'nogo lecheniia.

Drug treatment of cerebrovascular disorders alone and in combination with UV irradiation of autoblood gave rise to a positive trend in clinical and functional parameters more noticeable in the combined treatment. Also, there was a fall in red cell levels of malonic dialdehyde. A course of speleotherapy given to children with bronchial asthma contributed to normalization of free radical oxidation and reestablishment of molecular structure in red cell membranes.

Hyperhomocyst(e)inemia--determining factors and treatment.

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

Homocysteine: evidence for a causal relationship with cardiovascular disease.

Elevated plasma homocysteine levels are associated with vascular disease and thrombosis. Premature atherosclerosis and thromboembolism are seen in children who are homozygotes for defects in enzymes responsible for the metabolism of homocysteine. Adults with heterozygous defects have less marked elevations of homocysteine, and onset of atherosclerosis and vascular disease are delayed into the fourth and fifth decade of life. Homocysteine can damage vascular endothelium, cause proliferation of vascular smooth muscle, activate platelets, promote lipid peroxidation, and activate the coagulation cascade. Epidemiologic studies have linked elevations in plasma homocysteine with coronary artery disease, cerebrovascular disease, and thromboembolism. Folic acid, in combination with vitamins B6 and B12, can normalize homocysteine levels in most patients. Although randomized trials assessing the efficacy of homocysteine reduction have yet to be completed, treatment with vitamin supplementation should be considered in all patients at risk for vascular disease.

[The role of hyper-homocysteinemia in the etiology of some vascular diseases]. / Hyperhomocysteinaemia szerepe az egyes érrendszeri betegségek kóreredetében.

About 5% of population have a highly, while other 15% a moderately elevated plasma homocysteine level. Hyperhomocysteinemia may be responsible about 10-20% of coronary artery, 40% of cerebrovascular and 60% of peripheral vascular diseases. There in an inverse relationship between folate, cobalamin and pyridoxine intake or blood level and plasma homocysteine level. In addition, the intake of these three B vitamins can reduce high plasma homocysteine level. Folate-folic acid seems to be the most important in homocysteine reduction due to the compensation of thermolabile methylenetetrahydrofolate reductase insufficiency, however, a milder impact of cobalamin any pyridoxine (mainly following a methionine load test) is also proved. There are possibilities to reduce risk associated with elevated homocysteine: e. g. dietary supplementation or food fortification. In Hungary bread enriched by folic acid, cobalamin and pyriodixine might reduce rate of vascular diseases due to hyperhomocysteinemia.