Hyperhomocysteinemia as an Independent Risk Factor for Cardioembolic Stroke in the Turkish Population (original) (raw)
Related papers
Homocysteine metabolism, hyperhomocysteinaemia and vascular disease: An overview
Journal of Inherited Metabolic Disease, 2006
Hyperhomocysteinaemia has been regarded as a new modifiable risk factor for atherosclerosis and vascular disease. Homocysteine is a branch-point intermediate of methionine metabolism, which can be further metabolised via two alternative pathways: degraded irreversibly through the transsulphuration pathway or remethylated to methionine by the remethylation pathway. Both pathways are B-vitamin-dependent. Plasma homocysteine concentrations are determined by nongenetic and genetic factors. The metabolism of homocysteine, the role of B vitamins and the contribution of nongenetic and genetic determinants of homocysteine concentrations are reviewed. The mechanisms whereby homocysteine causes endothelial damage and vascular disease are not fully understood. Recently, a link has been postulated between homocysteine, or its intermediates, and an alterated DNA methylation pattern. The involvement of epigenetic mechanisms in the context of homocysteine and atherosclerosis, due to inhibition of transmethylation reactions, is briefly overviewed.
Impaired Homocysteine Metabolism and Atherothrombotic Disease
Laboratory Investigation, 2001
Based on recent retrospective, prospective, and experimental studies, mild to moderate elevation of fasting or postmethionine-load plasma homocysteine is accepted as an independent risk factor for cardiovascular disease and thrombosis in both men and women. Hyperhomocysteinemia results from an inhibition of the remethylation pathway or from an inhibition or a saturation of the transsulfuration pathway of homocysteine metabolism. The involvement of a high dietary intake of methionine-rich animal proteins has not yet been investigated and cannot be ruled out. However, folate deficiency, either associated or not associated with the thermolabile mutation of the N 5,10 -methylenetetrahydrofolate reductase, and vitamin B 6 deficiency, perhaps associated with cystathionine -synthase defects or with methionine excess, are believed to be major determinants of the increased risk of cardiovascular disease related to hyperhomocysteinemia. Recent experimental studies have suggested that moderately elevated homocysteine levels are a causal risk factor for atherothrombotic disease because they affect both the vascular wall structure and the blood coagulation system. The oxidant stress that results from impaired homocysteine metabolism, which modifies the intracellular redox status, might play a central role in the molecular mechanisms underlying moderate hyperhomocysteinemia-mediated vascular disorders. Because folate supplementation can efficiently reduce plasma homocysteine levels, both in the fasting state and after methionine loading, results from further prospective cohort studies and from on-going interventional trials will determine whether homocysteine-lowering therapies can contribute to the prevention and reduction of cardiovascular risk. Additionally, these studies will provide unequivocal arguments for the independent and causal relationship between hyperhomocysteinemia and atherothrombotic disease. (Lab Invest 2001, 81:645-672).
Metabolism of homocysteine and its relationship with cardiovascular disease
Journal of thrombosis and …, 2004
Hyperhomocysteinemia, or the rise of plasmatic homocysteine levels above 15 µg/dL, is accepted nowadays as an independent risk factor for cardiovascular disease in men and women. Homocysteine (Hcy) is a non-protein forming aminoacid (aa) derivated from the loss of the methyl group, found within methionine. Methionine regenerates by retrieving the methyl radical from 5-methyltetrahydrofolate (5-MTHF) creating tetrahydrofolate (THF) which will then regenerate to 5-MTHF through the action of methylentetrahydrofolate reductase (MTHFR). This process is called remethylation. Alternatively, Hcy can follow the transsulfuration route, where through cystationine-β-syntetase (CBS), it irreversibly converted into cystationine, a precursor of cysteine, glutathione, and other substances that are finally excreted in the urine. Hyperhomocysteinemia results from inhibition of the remethylation route, or inhibition or saturation of the transsulfuration pathway. Main factors causally associated increased plasmatic Hcy are mutations of the enzymes MTHFR and CBS; varying nutritional and health states; demographic factors; and, others. The most accepted hypotheses about Hcy action in cardiovascular disease are direct endothelial and vessel wall damage; oxidative stress generation; and, stimulation of a procoagulant and proinflammatory state of blood components. Since hyperhomocysteinemia can be effectively treated with folic acid, prospective trials are underway to determine if folate therapy is required to lower Hcy levels in plasma. These studies also attempt to address the impact, if any, of folate therapy in the reduction of cardiovascular risk, and to demonstrate if hyperhomocysteinemia is actually an independent risk factor that can be effectively treated.
Ischemic stroke and hyperhomocysteinemia: truth or myth?
Acta neurologica Belgica
It is useful to determine homocysteine levels for stroke who present no clue for vascular disease and thrombosis, who have an ischemic stroke at a young age and who have a family history of premature atherosclerosis. Because of the low cost and safety of the therapy, the American Heart and Stroke Association advises to treat patients with a stroke and hyperhomocysteinemia daily with 0,4 mg folic acid, 2,4 µg vitamin B12 and 1,7 mg vitamin B6. A significant benefit in secondary prevention is not yet proven. The results of larger follow-up trials have to be published.
2016
Cerebrovascular stroke is complex heterogeneous multifactorial disorder associated with number of risk factors, including diabetes mellitus,hypertension, tobacco smoking or chewing; etc. MethylenetetrahydroFolate reductase (MTHFR) enzyme is one of the main regulatory enzymerequired for the metabolism of homocysteine. An impaired function of this metabolic pathway leads to accumulation of homocysteine in blood. The elevation of plasma total homocysteine and deficiency of B-vitamins such as folic acid and vitamin B12 factors associated with increased cardiovascular cerebrovascular and thromboembolic risk. A single nucleotide polymorphism of the MTHFR gene C677T causes reduction in enzyme activity. In the current study, we determined the prevalence of C677T mutation andcorrelated them to plasma total homocysteine, folic acid and vitaminB12. Total 50 cerebral stroke patients and 50 normal, healthy subjects acting as controls were taken for the study. The total homocysteine level in plasma was determined by high performance liquid chromatography (HPLC). Plasma level of folic acid and vitamin B12were estimated by competitive immunoassay using direct chemiluminescence technology. ARMS PCR was used toexamine MTHFR C677T polymorphism. Result shows concentration of significantly low plasma Folatelevels,whereas vitamin B12 does notshow any significant differencein patients than controls.Total homocysteine concentrations in plasma were significantly higher in stroke as compared to controls. The variation in gene of MTHFR C677T and reduced level of B-vitamins have been related to hyperhomocysteinemia.
Study on Homocysteinemia as a Risk Factor of Ischemic Stroke
TAJ: Journal of Teachers Association, 2021
Despite recent advances, only two-third of all strokes can be attributed to known causal risk factors. Homocysteine (tHcy), a sulfur-containing amino acid, is now considered to be an important risk factor for vascular diseases, along with the established risk factors like hyperlipidemia, hypertension, diabetes mellitus, and smoking. Elevated homocysteine levels play a causal role in the pathogenesis of atherosclerosis, thromboembolism and vascular endothelial dysfunction with an increased incidence of ischemic stroke. This study aimed to find out the association of hyperhomocysteinemia with ischemic stroke. A total of 100 subjects were included in this study, 50 were ischemic stroke patients enrolled as case, and 50 were normal healthy individuals enrolled as control. Serum homocysteine level was measured in both case and control groups. The comparison was made in both groups regarding other common risk factors like diabetes mellitus, hypertension, smoking, dyslipidemia, family his...
Hyperhomocysteinemia as a risk factor for ischemic stroke: An Indian scenario
Neurology India, 2005
Background: Hyperhomocysteinemia has been proposed as an important risk factor for ischemic stroke worldwide, but data available from the Indian subcontinent is scarce. Aim: To study homocysteine levels in patients with ischemic stroke and compare it with age-and sex-matched controls. Settings and Design: Case-control prospective study. Materials and Methods: Fifty-seven patients with ischemic stroke and 30 controls were recruited for the study. They were subdivided into two subgroups (<40 years and >40 years of age) and plasma fasting total homocysteine (tHcy) levels were measured. Statistical analysis used: Student's 't' test and chisquare test. Results: The tHcy were significantly high in patients with stroke, compared to controls (9.91 ± 2.25 vs 8.00 ± 2.74 µmol/l; P < 0.001). Significantly high levels were seen in both male patients compared to controls (10.24 ± 2.34 vs 8.45 ± 2.72 µmol/l; P = 0.01) and female patients compared to controls (9.08 ± 1.81 vs 6.79 ± 2.60 µmol/l; P = 0.04). The tHcy levels were significantly high in patients with hypertension compared to normotensive patients (10.96 vs 9.49 µmol/ l; P = 0.01) and smokers compared to nonsmokers (11.17 vs 9.33 µmol/l; P = 0.01). Conclusions: Hyperhomo-cysteinemia emerged as an important independent risk factor for ischemic stroke. A strong positive correlation was also observed between hypertension, smoking, and high-tHcy levels in the present study.
Homocysteine- The Hidden Factor and Cardiovascular Disease: Cause or Effect?
Biochemistry & Analytical Biochemistry
Markedly or mildly elevated circulating homocysteine concentrations are associated with increased risk of vascular occlusion. Here we review possible mechanisms that mediate these effects. Inborn errors of homocysteine metabolism result in markedly elevated plasma homocysteine (200-300 μmol/L) and thromboembolic (mainly venous) disease which is easily normalized with oral folate and ongoing trials are assessing the effect of folate treatment on outcomes. Some people have a common genetic variant (called methylenetetrahydrofolate reductase, abbreviated MTHFR) that also impairs their ability to process folate. Indeed, there are evidences suggesting an acute antioxidant effect of folic acid on homocysteine concentrations. This antioxidant mechanism may oppose an oxidant effect of homocysteine and be relevant to treatment of patients with vascular disease, especially those with chronic renal insufficiency. Such patients have moderately elevated plasma homocysteine and greatly increased cardiovascular risk that is largely unexplained.