Homocysteine Concentrations In Patients Research Articles

Effect of B vitamins supplementation on cardio-metabolic factors in patients with stable coronary artery disease: A randomized double-blind trial.

This study aimed to evaluate whether B vitamins supplementation would improve dyslipidemia, alleviate inflammatory state of patients with stable coronary artery disease (SCAD). We conducted a randomized, double-blind, 12-week, placebo-controlled trial involving adults with SCAD, and who were randomly divided into B vitamins group (folic acid and VB-6) and control group (placebo tablet). Blood tests had also been performed at baseline and endpoint. After 12 weeks of intervention, B vitamins supplementation significantly improved the concentration of serum TG, TC and HDL-C (p<0.05). Changes of serum homocysteine in B vitamins treatment were significantly different compared to placebo by the multivariate-adjusted analysis (3.02±2.35 vs 1.55±1.58 p<0.001). Meanwhile, the levels of IL-1β and IL-10, significant difference were observed between two groups after adjustment for confounding factors. Supplementation with B vitamins significantly improves lipid metabolism, alleviate inflammation and serum homocysteine concentration in patients with SCAD.

T-cell subsets are associated with serum homocysteine concentration in patients with essential hypertension

ABSTRACTObjective: To explore the association between serum homocysteine (Hcy) concentration and T-cell subsets from patients with essential hypertension. Patients and Methods: A total of 218 essential hypertension patients were recruited, of which 170 were H-type essential hypertensive and 48 were non-H-type essential hypertensive. H-type essential hypertensive patients were divided into three groups by concentration of serum Hcy. The peripheral blood T-cell subsets (CD3+%, CD4+%, CD8+ T%, CD4+/CD8+) and clinical features including age, sex, serum creatinine, uric acid, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were recorded and analyzed with T-cell subsets which were counted by fluorescence activated cytometry. Results: Compared with non-H-type hypertensive patients, CD4+ T-cell percentage in peripheral blood was significantly decreased in H-type hypertensive patients. Because of the increase of Hcy level, CD4+ T-cell percentage decreased. Linear regression analysis showed that Hcy level was negatively correlated with CD4+ T-cell percentage; however, it was positively correlated with CD3+ T-cell percentage. Conclusion: A direct association between serum Hcy concentrations and T-cell percentage was observed in patients with essential hypertension. This observation indicates that T-cell subsets might play an important role in hypertension.

Vitamin B‐6 supplementation might mediate antioxidant capacity by reducing plasma homocysteine concentration in patients with hepatocellular carcinoma after tumor resection

Deficient vitamin B‐6 status might be a causative factor for hepatocellular carcinoma (HCC) development, it would be useful to determine whether vitamin B‐6 supplementation would have a preventive effect in reducing plasma homocysteine, or indirectly increasing glutathione and its dependent antioxidant enzyme capacities in patients with HCC. The purpose of this study was to investigate whether vitamin B‐6 supplementation had a significant effect on plasma homocysteine, oxidative stress, and antioxidant capacities in HCC patients following tumor resection. Thirty‐three HCC patients were included in the study. Patients were randomly assigned to either the placebo (n = 16) group or the vitamin B‐6 50 mg/d (n = 17) group for 12 weeks. Plasma homocysteine in the vitamin B‐6 group was significantly decreased at week 12, while the level of trolox equivalent antioxidant capacity (TEAC) was significantly increased at the end of the intervention period. Vitamin B‐6 supplementation had significant reducing effect on the change of plasma homocysteine (β = −2.4, p = 0.02) but not on the change of TEAC level after adjusting for potential confounders. The change of plasma homocysteine was significantly associated with the change of TEAC after adjusting for potential confounders (β = −162.0, p = 0.03). Vitamin B‐6 supplementation seemed to mediate antioxidant capacity via by reducing plasma homocysteine rather than having a direct anti‐oxidative effect in HCC patients who had recently undergone tumor resection.Support or Funding InformationThis study was supported by the Ministry of Science and Technology, Taiwan (MOST 104‐2320‐B‐040‐009‐MY3).

Vitamin B-6 Supplementation Could Mediate Antioxidant Capacity by Reducing Plasma Homocysteine Concentration in Patients with Hepatocellular Carcinoma after Tumor Resection.

Vitamin B-6 has a strong antioxidative effect. It would be useful to determine whether vitamin B-6 supplementation had effects on antioxidant capacities in patients with hepatocellular carcinoma (HCC) who had recently undergone tumor resection. Thirty-three HCC patients were randomly assigned to either the placebo (n = 16) group or the vitamin B-6 50 mg/d (n = 17) group for 12 weeks. Plasma pyridoxal 5′-phosphate, homocysteine, indicators of oxidative stress, and antioxidant capacities were measured. Plasma homocysteine in the vitamin B-6 group was significantly decreased at week 12, while the level of trolox equivalent antioxidant capacity (TEAC) was significantly increased at the end of the intervention period. Vitamin B-6 supplementation had a significant reducing effect on the change of plasma homocysteine (β = −2.4, p = 0.02) but not on the change of TEAC level after adjusting for potential confounders. The change of plasma homocysteine was significantly associated with the change of TEAC after adjusting for potential confounders (β = −162.0, p = 0.03). Vitamin B-6 supplementation seemed to mediate antioxidant capacity via reducing plasma homocysteine rather than having a direct antioxidative effect in HCC patients who had recently undergone tumor resection. The clinical trial number is NCT01964001, ClinicalTrials.gov.

Vitamin B12 levels are not affected by radioiodine ablation of the thyroid.

Radioiodine administered for the treatment of hyperthyroidism and thyroid cancer can be taken up by many non-thyroid tissues which express sodium iodide symporter. Though gastric mucosa takes up radioiodine, its impact on parietal cell has not been evaluated. The aim of the present study was to compare vitamin B12 and homocysteine concentrations in patients with thyroid disorders treated by radioiodine ablation with those in control population without radioiodine exposure. Patients with Graves' disease, toxic multinodular goiter (TMNG), toxic adenoma (TA) or differentiated thyroid cancer (DTC) who had received 131I were included as "patients". Healthy persons and patients having Graves' disease but without exposure to radioiodine were recruited as "controls". A total of 35 patients and 35 controls were included. Patients were divided into Graves' disease and non-Graves' disease (TMNG, TA, DTC) groups. Graves' disease patients were compared with Graves' disease controls while non-Graves' disease patients were compared with healthy controls. In the Graves' disease group, median vitamin B12 concentration was 240 pg/ml (IQR: 148 - 371) in patients (n=23) and 195 pg/ml (IQR: 140 - 291 pg/ml) (p=0.13, ns) in controls (n=24). In the non-Graves' disease group, median serum vitamin B12 concentration was 147 pg/ml (IQR: 124 - 325pg/ml) in patients (n=12) and 190 pg/ml (IQR: 157 - 373 pg/ml) (p=0.34, ns) in healthy controls (n=11). Homocysteine concentrations were also similar in compared groups of patients and controls. Radioiodine ablation does not cause vitamin B12 deficiency. However, a prospective study with a larger number of patients is required to confirm this finding.

GW24-e1838 Efficacy of folic acid supplementation alone on endothelial function and plasma homocysteine concentration in coronary artery disease: a meta-analysis of randomised controlled trials

ObjectivesOur purpose is to conduct an updated meta-analysis of relevant randomised controlled trials (RCTs) to estimate the effect of folic acid supplementation alone on endothelial function and plasma homocysteine concentration...

PP159—C677T Polymorphism of Methylenetetrahydrofolate Reductase and Homocysteine Concentration in Patients with Essential Hypertension

e68 Volume 35 Number 8S Among Costa Ricans, CYP2C9*2 was also lower in the AM than in the CRM population (P < 0.05). Moreover, the frequency of CYP2C9*3 in the CRM, AM and AC groups was 3.6%, 2.1% and 3.3%, respectively. CYP2C9*6 was not detected. Conclusion: Present data support that the CYP2C9*2 frequency is lower in Amerindian populations than Caucasians, suggesting the importance of pharmacogenetic studies for optimizing drug dosages in different populations according to their ancestry. Funding Sources: This study was supported by the University of Costa Rica (CCG, GJA and RB), AEXCID Cooperacion Extremena of Junta de Extremadura (11A002), Consejeria de Empleo, Empresa e Innovacion and Fondo Social Europeo (FSE) Grant PD10199 (MEGN) and the Network Red Iberoamericana de Farmacogenetica y Farmacogenomica. PI10/02758. Disclosure of Interest: None declared.

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and variations of homocysteine concentrations in patients with Behcet's disease

BackgroundBehcet's disease (BD) is a chronic, relapsing, multi-systemic inflammatory disorder of unknown causes. This disease is mainly characterized by mucocutaneous, ocular, vascular, and central nervous system manifestations. The aim of this study is to investigate the associations between C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and the plasma homocysteine (Hcy), folate, and B12 levels in a relatively large cohort of Tunisian patients with BD. MethodsThe study included 142 patients with BD and 172 healthy controls. The C677T and A1298C polymorphisms were genotyped using PCR-RFLP. Serum Hcy level was determined using a fluorescence polarization immunoassay. Serum folate and vitamin B12 levels were measured by electrochemiluminescence immunoassay. ResultsGenotype and allele frequencies of the two studied MTHFR polymorphisms did not show any significant differences among BD patients compared to controls. Patient carriers of the 677TT variant and the 677T allele displayed significantly higher Hcy concentration. Moreover, no significant association was found between neither A1298C polymorphism nor the C allele and Hcy, folate, and B12 levels. In multivariate analyses, we reported that 677T allele, male gender, and creatinine level were independent risk factors for hyperhomocysteinemia (HHC). ConclusionsIn the present study, we report the absence of any significant differences between genotype and allele frequencies for both studied polymorphisms among BD patients compared to healthy controls. Besides, we showed that the T allele of MTHFR C677T polymorphism influenced the Hcy level which is an independent risk factor for HHC in Tunisian BD patients.

The Relationship between Plasma Homocysteine and Early Coronary Collateral Vessel Development after Acute Myocardial Infarction

Aim: Homocysteine is known to inhibit endothelial cell proliferation, which is a key event in angiogenesis. Factors responsible for the presence or absence of coronary collateral circulation are poorly understood. Therefore, in this study we investigated the effect of plasma homocysteine level on the early formation of angiographically visible collaterals after acute myocardial infarction. Materials and Methods: The study included 60 patients that had ST-segment elevation myocardial infarction (STEMI). All the patients underwent coronary angiography 1-4 days after admission (mean: 2.3 ± 1.2 days). Patients were graded according to Rentrop classification. Patients with grade 0 or 1 collateral vessels were classified as poor collaterals; patients with grade 2 or 3 collateral vessels were classified as good collaterals. Results: In all, 35 (58.3%) patients had poor collateral vessel filling and the remaining 25 (41.7%) patients had good collateral filling. Plasma homocysteine concentration in patients with poor and good collateral formation was 18.2 ± 8.6 µmol/l and 12.7 ± 2.4 µmol/l, respectively (P = 0.008). There was a negative linear correlation between Rentrop subclasses and plasma homocysteine concentration (r = –0.391, P = 0.002). We assessed the effect of demographic variables, such as age, gender, hypertension, diabetes mellitus, smoking, lipid parameters, and plasma homocysteine concentration, on the development of collaterals. The only independent variable that affected the development of collaterals was homocysteine level (OR: 0.71; 95% CI = 0.57-0.89, P = 0.003). Conclusions: This study demonstrates for the first time that there is an inverse relationship between the early development of collateral circulation after acute myocardial infarction and plasma homocysteine concentration.

Comparative analysis of homocysteine concentrations in patients with retinal vein occlusion versus thrombotic and atherosclerotic disorders

The objectives of the present study were to determine the concentrations of plasma homocysteine in a large (n = 562) cohort of patients with retinal vein occlusion (RVO) and to compare them with the values observed in other vascular thrombotic and atherosclerotic conditions. Results were compared with those observed in patients with deep vein thrombosis (n = 1700), pulmonary embolism (n = 542), transient ischemic attack (n = 1301), cerebrovascular accident (n = 1299), myocardial infarction (n = 3087), as well as peripheral artery occlusive disease (n = 1946). No differences were found between the age-adjusted estimated marginal mean +/- SE for homocysteine concentrations in individuals with RVO and in those who had other atherosclerotic and atherothrombotic diseases The respective concentrations for RVO, deep vein thrombosis, pulmonary embolism, transient ischemic attack, cerebrovascular accident, myocardial infarction, and peripheral artery occlusive disease were 13.8 +/- 0.4, 14.7 +/- 0.3, 14.3 +/- 0.5, 14.2 +/- 0.3,14.6 +/- 0.3, 13.8 +/- 0.2, 14.4 +/- 0.2 pmol/l for men and 11.4 +/- 0.4, 10.7 +/- 0.2, 10.8 +/- 0.3, 10.8 +/- 0.2, 11.8 +/- 0.2, 11.2 +/- 0.2 pmol/l for women. In conclusion, the concentrations of homocysteine observed in patients with RVO are similar to those detected in other thrombotic and atherosclerotic vascular disorders. In view of the fact that this is a common disorder of the elderly, increased homocysteine concentrations often reported in patients with RVO could reflect the underlying atherothrombotic condition and might not necessarily be specifically related to the RVO per se. This information is relevant in researching the potential etiopathologic role, if any, of increased homocysteine concentrations in RVO.

Hyperhomocysteinemia in Inflammatory Bowel Disease Patients Without Past Intestinal Resections

Homocysteine is a sulfur-containing amino acid formed during the demethylation of methionine and high levels of this amino acid is a known risk factor for both arterial and also venous thromboembolic complications. Deficiencies of cobalamin, folate, and pyridoxine may predispose subjects to hyperhomocysteinemia, a common phenomenon in inflammatory bowel disease (IBD) patients. The aim of this study was to identify the prevalence, risk factors of hyperhomocysteinemia and its correlation with prior thromboembolic events in an IBD cohort without past intestinal resections. In this prospective study, we studied the concentrations of homocysteine, cobalamin, folate, and pyridoxine in 105 consecutive patients with IBD, of whom 11 had a prior history of thromboembolic complications. Data regarding smoking habits, medication use, disease location, and severity were gathered and patients with past intestinal resections were excluded. Age-matched and sex-matched 85 healthy volunteers served as controls and multivariate regression analysis was performed to find out independent predictors of hyperhomocysteinemia. The mean age (+/-SD) in the IBD cohort was 38.69+/-12.13 years, and 51% were male. The mean age in the control group was 37.61+/-10.05 years, and 52% were male. Homocysteine concentrations in patients were higher [16.35 micromol/L (range 6.82 to 48.15) vs. 9.60 micromol/L (range 4.97 to 17.39), P=0.000] and hyperhomocysteinemia had a higher prevalence in patients than in the controls (56.2% vs. 4.7%, chi2=56.179, P=0.000), thus IBD significantly increased the risk of hyperhomocysteinemia [odds ratio=25.973 (95% confidence interval: 8.861-76.128)]. Homocysteine concentrations in patients with a history of thrombosis were not higher than those without a history of thrombosis [16.29 micromol/L (range 8.45 to 34.75) vs. 16.36 micromol/L (range 6.82 to 48.15), not significant]. Hyperhomocysteinemia was found in 54.5% of patients with thrombosis and 56.4% of patients without thrombosis (not significant). On stepwise regression analysis, plasma cobalamin level, albumin concentration, erythrocyte sedimentation rate, and platelet count were found to be independent predictors of elevated homocysteine levels. IBD patients have a higher prevalence of hyperhomocysteinemia than do healthy controls and elevated homocysteine levels are independently associated with lower serum cobalamin, albumin levels and elevated erythrocyte sedimentation rate, and platelet count. There is no correlation between hyperhomocysteinemia and a history of prior thromboembolic events.

Plasma and Vitreous Homocysteine Concentrations in Patients With Proliferative Diabetic Retinopathy

An increase in plasma concentrations of homocysteine (Hcy) in proliferative diabetic retinopathy (PDR) has been described. The aim of this study was to investigate vitreous Hcy levels in patients with PDR. Plasma and vitreous samples were obtained simultaneously at the time of vitreoretinal surgery from 20 patients with PDR and 12 nondiabetic patients with nonproliferative ocular diseases. Hcy levels were determined by high-performance liquid chromatography. The mean vitreous and plasma Hcy concentrations for the diabetic group were 3.64 +/- 0.65 micromol/L and 16.04 +/- 2.75 micromol/L, respectively. The mean intravitreal and plasma Hcy concentrations for the control group were 1.08 +/- 0.45 micromol/L and 9.18 +/- 3.91 micromol/L, respectively. Both plasma and vitreous Hcy concentrations for the diabetic group were significantly higher than those for the control group (P < 0.001). A statistically significant correlation between vitreous and plasma Hcy concentrations was present only for the diabetic group (r = 0.525; P = 0.017). Vitreous Hcy concentrations were elevated in patients with PDR probably due to breakdown of the blood-retina barrier.

Low vitamin B6, and not plasma homocysteine concentration, as risk factor for abdominal aortic aneurysm: A retrospective case–control study

Hyperhomocysteinemia has been associated with vascular disease in many epidemiologic studies, but only a few have reported on the relation between hyperhomocysteinemia and aneurysms of the abdominal aorta (AAAs). Although these studies showed higher homocysteine concentrations in patients with AAA than in controls, little attention had been given to possible confounding factors. Most patients with AAA are of older age, have an impaired renal function, and have other risk factors for cardiovascular disease. This matched case-control study investigated the relation between homocysteine concentration (before and after methionine loading) and AAA, taking into account possible confounders such as age, sex, and concentrations of creatinine and B vitamins. Patients with a history of AAA were recruited from the outpatient clinic; 60% had already undergone surgery for their AAA. They were asked to invite a friend or neighbor to participate as a control subject (age-matched and sex-matched). Concentrations of homocysteine, vitamin B6, vitamin B12, folate, and creatinine were determined in the fasting state, and blood was taken for methylenetetrahydrofolate reductase (MTHFR) mutation analysis. Six hours after oral methionine loading, the postmethionine load homocysteine concentration was determined. Univariate analysis showed an odds ratio (OR) of 2.2 (95% confidence interval (CI), 0.9 to 5.5) for the risk of AAA for the highest quartile of homocysteine concentration. After adjustment for creatinine, the OR was markedly reduced to 1.24 (95% CI, 0.42 to 3.66), and this risk further attenuated in the multivariate analysis. Univariate analysis of the B vitamins showed an increased risk of AAA for the bottom quartile of vitamin B6 (OR, 3.75; 95% CI, 1.22 to 11.54), which even increased after adjustments. The relative risk associated with the MTHFR 677TT polymorphism was 2.1 (95% CI, 0.9 to 5.3). Vitamin B6, but not homocysteine, is an independent risk factor for AAA. The role of vitamin B6 in the pathogenesis of AAA needs to be further elucidated.

Effects of 1 Year of Treatment with Pioglitazone or Rosiglitazone Added to Glimepiride on Lipoprotein (a) and Homocysteine Concentrations in Patients with Type 2 Diabetes Mellitus and Metabolic Syndrome: A Multicenter, Randomized, Double-Blind, Controlled Clinical Trial

Background: Although the metabolic effects of the thiazolidinediones have been well studied, there is a lack of comparative data on their effects on certain cardiovascular risk factors, such as elevated plasma levels of lipoprotein (a) (Lp[a]) and homocysteine (Hcy). Objective: This study compared the effects of pioglitazone or rosiglitazone added to glimepiride on a range of lipid parameters, focusing on Lp(a) and Hcy, in patients with type 2 diabetes mellitus and the metabolic syndrome. Methods: This was a multicenter, randomized, controlled, double-blind study in patients with type 2 diabetes and the metabolic syndrome (hypertension [≥130/85 mm Hg]) and triglyceridemia (≥150 mg/dL). In addition to glimepiride 4 mg/d, patients received pioglitazone 15 mg QD or rosiglitazone 4 mg QD for 1 year. The primary efficacy variables were change from baseline in body mass index (BMI), glycosylated hemoglobin (HbA 1c), Lp(a), and Hey. Secondary efficacy measures were changes in fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) concentrations, fasting and postprandial insulin concentrations (FPI and PPI, respectively), the Homeostasis Model Assessment index, and the lipid profile (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides). All these parameters were measured after a 12-hour fast every 3 months for 1 year. Tolerability was assessed based on reported adverse events and laboratory abnormalities at each study visit. Results: Ninety-one white patients with type 2 diabetes and the metabolic syndrome were enrolled, and 87 completed the study (43 men, 44 women; mean [SD] age, 53 [6] years; mean weight, 68.4 [3.3] kg). Mean baseline values for BMI and HbA 1c were 24.3 (0.8) kg/m 2 and 8.1 % (0.8 %), respectively. At the end of 1 year, both treatment groups had significant increases from baseline in BMI (4.9% glimepiride + pio glitazone, 6.2% glimepiride + rosiglitazone; P < 0.05). Glimepiride + pioglitazone was associated with the following percent improvements from baseline in measures of glycemic control: −17.1% in HbA 1c, −19.3% in FPG, −17.8% in PPG, −40.1% in FPI, and −22.6% in PPI (all, P < 0.01). The corresponding percent improvements from baseline with glimepiride + rosiglitazone were −16.3%, −19.9%, −15.0%, −44.8%, and −22.1% (all, P < 0.01). There were no significant differences between treatment groups in any of these parameters. The pioglitazone group had significant improvements from baseline in TC (−11.1%), LDL-C (−12.0%), HDL-C (15.0%), and triglycerides (22.4%) (all, P < 0.05), whereas the rosiglitazone group had significant increases in TC (14.9%), LDL-C (16.5%), and triglycerides (17.9%) (all, P < 0.05); the difference between pioglitazone and rosiglitazone was statistically significant ( P < 0.05). The change from baseline in Lp(a) was significant in the pioglitazone group, both relative to baseline and compared with the rosiglitazone group (−19.7% vs 0.5%, respectively; P < 0.05 vs baseline and vs rosiglitazone). Changes from baseline in Hey were significant in both the pioglitazone and rosiglitazone groups (−20.2% and −25.0%, respectively; P < 0.05), with no significant difference between groups. Both treatments were well tolerated, and no patients had significant changes in transaminases. Conclusions: In these patients with type 2 diabetes and the metabolic syndrome, the combinations of glimepiride with pioglitazone and glimepiride with rosiglitazone produced significant improvements in measures of glycemic control, plasma lipids, and homocysteinemia. One year of treatment with the pioglitazone combination was associated with significantly reduced plasma Lp(a) levels compared with the rosiglitazone combination.

The Influence of 3 Weeks Therapy with Continuous Positive Airway Pressure on Serum Leptin and Homocysteine Concentration in Patients with Obstructive Sleep Apnea Syndrom

Obstructive sleep apnea (OSA) is one of the most often sleep disturbance. Not treated patients have 2–3 times more risk for death because of the cardiovascular diseases. Leptin and homocysteine are the risk factors for cardiovascular diseases. Treatment by nCPAP has positive influence for health care and reduction of hyperten-sion in this group. The aim of this study was to evaluate an effect of 3 weeks nCPAP therapy on a serum leptin and homocysteine con-centrations in patients with OSA. Material and methods: The study group consisted of 48 male patients in the age x = 51.2 ± 7.5 years old, OSA was diagnosed by polisomnographic study The leptin concentration was evaluated by RIA methods (HUMAN LEPTIN RIA KIT), the homocysteine concentration was evaluated by Axis Homocysteine EIA test. Patients were treated by nCPAP during 3 weeks. Only 29 patients were effectively treated for this time. The compliance was: 5.07 ± 1.81 h. Results: In the group of 29 patients the serum leptin and homocysteine concentration before and after treatment were 11.05 ± 5.59 ng/mL vs. 11.07 ± 7.16 ng/mL i 10.98 ± 2.79 μmol/L vs. 10.34 ± 2.99 μmol/L. In the all study group the statistical important correlation between leptin and AHI, mean and minimal saturation overnight, fibrinogen econcentration, BMI, WHR, waist circumference, heart rate and between homocysteine and heart rate were observed. Conclusions: 3 weeks therapy does not have any effect on leptin and homocysteine concentrations in the studied group of patients with OSA. Serum leptin concentration correlates with AHI, TMB90, as well as with mean and minimal saturation during a sleep. This indicates a potentially higher risk of cardiovascular diseases in the studied group.

The screening power of methylenetetrahydrofolate reductase C677T polymorphism versus plasma homocysteine concentration in patients with stenosis of the internal carotid artery

BackgroundHyperhomocysteinemia is an important and independent risk factor for vascular disease. About 35% of patients with stroke and 47% of patients with peripheral arterial disease have elevated plasma homocysteine (HCY) concentrations. The relationship between plasma HCY and the methylentetrahydrofolate reductase (MTHFR) C677T polymorphism is still unclear, especially in regard to screening/diagnostic power.MethodsThis case-control study was performed on 96 patients, who underwent surgery due to asymptomatic or symptomatic high grade stenosis of the internal carotid artery (ICA), and 96 healthy age and sex-matched, controls. Plasma HCY concentration was determined using a commercial kit for fully automated analysis (AxSYM, Abbott). The C677T polymorphism of the MTHFR-gene was assessed by PCR.ResultsThe mean plasma HCY concentration was significantly higher in the group with stenosis of ICA compared to the controls, 12.43 ± 6.96 μM and 10.16 ± 3.16 μM, respectively, (p < 0.05). An HCY plasma concentration of 1.5 SD above the mean value of the control group, was defined as cut-off for a pathological versus physiological plasma concentration. The sensitivity and specificity of HCY was 0.27 and 0.94, respectively. The positive predictive value was 0.82. There was no significant difference in the frequency of the MTHFR 677 CT and TT genotype between patients and controls (47% vs. 47% and 8.3% vs. 11.4%, respectively). Carriers of the T-allele (CT and TT genotypes) have significantly higher plasma HCY concentrations than CC patients, 14.1 ± 7.6 μM and 10.29 ± 5.2 μM, respectively, p < 0.05. Sensitivity and specificity of the MTHFR C677T polymorphism (T-allele) were 0.56 and 0.40, respectively. The positive predictive value was 0.48. There was no significant difference in plasma HCY or genotype frequency of the MTHFR C677T polymorphism between asymptomatic and symptomatic patients.ConclusionOur study shows that in a population with a given pretest disease probability of 50%, the determination of plasma HCY concentration, with a positive predictive value of 0.82, is more suitable for screening of patients at risk than analysis of the MTHFR C677T polymorphism.

Elevated plasma homocysteine concentrations as a predictor of steatohepatitis in patients with non‐alcoholic fatty liver disease

Although steatosis is common in patients with severe hyperhomocysteinemia due to deficiency of cystathionine beta-synthase, there are no satisfactory data on homocysteine concentrations in patients with non-alcoholic fatty liver disease. The main aim of the present study was to evaluate the clinical significance of plasma homocysteine concentrations in patients with non-alcoholic fatty liver disease. Seventy-one non-alcoholic fatty liver disease patients, 36 patients with chronic viral hepatitis and 30 healthy persons were enrolled in the study. Homocysteine levels were measured by high-performance liquid chromatography. Insulin, folate, vitamin B(12) and lipoprotein levels were also determined in all groups. Homocysteine in the non-alcoholic fatty liver disease group was found to be significantly higher than other groups. Homocysteine was found to be significantly higher in the non-alcoholic steatohepatitis group when compared with simple steatosis group. A positive correlation was found between homocysteine and triglyceride, very-low-density-lipoprotein (VLDL) cholesterol, insulin, and index of insulin resistance in the non-alcoholic fatty liver disease group, and a negative correlation was found between homocysteine and folate, or vitamin B(12) in all groups. The homocysteine threshold for the prediction of steatohepatitis was 11.935 ng/mL. Furthermore; plasma homocysteine was a statistically significant predictor for severity of necroinflammatory activity in non-alcoholic steatohepatitis. The plasma homocysteine concentrations were significantly higher in patients with non-alcoholic fatty liver disease, while the concentrations were not affected by chronic viral hepatitis. Plasma homocysteine is a parameter for discriminating steatohepatitis from simple steatosis. Determining the plasma homocysteine concentrations may facilitate selection of steatosis patients in whom a liver biopsy should be performed.

Usefulness of Neopterin, C-reactive Protein, Homocysteine, Pyridoxal-5-phosphate, and Phospholipid Determination in Coronary Artery Disease

Abstract Blood serum neopterin, high sensitivity C-reactive protein (hsCRP), total homocysteine, pyridoxal-5-phosphatc ( P-5-P) and total phospholipid concentrations have been examined in 30 healthy individuals as well as in patients with coronary artery disease (CAD) verified by coronary angiography (43 patients with 1-artery disease, 24 patients with 2- or 3-artery disease, 17 patients with restenosis) before percutaneous transluminal coronary angioplasty. We have observed increased mean concentrations of neopterin, hsCRP and homocysteine as well as decreased mean concentration of P-5-P and phospholipids in all groups of CAD patients. The positive correlation between neopterin and hsCRP in all CAD patients (r = 0.536; Ρ &lt;0.01 ) as well as an increased frequency of these indices above the upper limit of normal during the course of CAD (30.1 % in eases with 1-artery disease, 54.2% of cases in 2- or 3-artery disease, 76.5% of cases in restenosis) allow to conclude that inflammation has a pivotal role in the progression of CAD. In restenosis the determination ot neopterin was of more significance than the determination of hsCRP. The combination of a mild increase of neopterin and homocysteine concentrations points to the worst prognosis of CAD, both after percutaneous transluminal coronary angioplasty and coronary bypass, restenosis was most liekly to appear. Mild increase of homocysteine concentration in patients with CAD docts not only indicate possible thickening of arterial wall and narrowing of lumen but also to impaired trans-sulfuration and remethylation pathways of homocysteine metabolism as well as to delayed methylation processes in the organism. A decrease of serum P-5-P concentration, which in all groups of CAD patiens reached about 50% as compared with healthy individuals, points to impairment of all metabolic processes, which require the biologically active form of vitamin B6 for their action. The decrease of mean serum phospholipid concentration in all groups of CAD patients may indicate both, impaired phospholipid biosynthesis due to delayed processes of methylation in the organism and increased loss of phosphatidylcholine necessary for transportation of oxidised low density lipoproteins into macrophages. Therefore the determination of serum phospholipid concentration and phosphatidylcholine concentration, especially, has the same significance in the course of CAD as the determination of total cholesterol, high and low density lipoprotein cholesterol widely used at present.

Influence of serum folic acid levels on plasma homocysteine concentrations in patients with rheumatoid arthritis

The purpose of this study was to investigate whether negative effects of methotrexate (mtx) on blood homocysteine (hmc) levels can be prevented with the replacement of folic acid. 42 female patients with rheumatoid arthritis (RA) were studied. Patients were separated into two groups according to their treatment status with mtx (group I: 27 patients taking mtx and folic acid; group II: 15 patients not using mtx). The level of hmc was found to be 6.3+/-2.4 micromol/l in group I and 7.87+/-3.2 micromol/l in group II (p>0.05). Folic acid levels of group I and II were found to be 21.3+/-15.9 ng/ml and 8.41+/-2.86 ng/ml respectively (p<0.001). There was a statistically-significant correlation between age and hmc levels (r=0.386, p=0.012). Negative statistically-significant correlations were observed between folic acid and hmc levels. The effects of mtx on hmc can be prevented with the replacement of folic acid.

C677T mutation of methylenetetrahydrofolate reductase gene and serum homocysteine levels in Turkish patients with coronary artery disease

Elevated levels of homocysteine is a risk factor for coronary artery disease. The C677T transition in methylenetetrahydrofolate reductase (MTHFR) is associated with increased homocysteine levels in the general population. We analysed the association between the MTHFR C677T polymorphism and serum homocysteine concentrations in patients with coronary artery disease (CAD). Allele frequencies for the 'C' (wild-type) and 'T' alleles were 0.71 and 0.29 in CAD patients and 0.70 and 0.30 in controls, respectively. There was no difference in the distribution of MTHFR genotypes between patients with CAD and control subjects (p > 0.05). In the patient group, homocysteine levels were higher than controls but not significantly (13.99 +/- 7.44 vs. 11.77 +/- 5.18 micromol l(-1); p > 0.05). Serum homocysteine concentration was significantly higher in the TT genotype with respect to CC and CT genotypes in both the control group (p < 0.01) and patient group (p < 0.01). Systolic and diastolic blood pressures in subjects with different MTHFR genotypes did not differ significantly. In conclusion, MTHFR C677T mutation was significantly related to hyperhomocysteinemia. In spite of the clear effect of the MTHFR polymorphism on elevated homocysteine levels, we did not observe any associations among the MTHFR genotypes with a the risk of CAD in the Turkish population.