Mean Plasma Total Homocysteine Research Articles

Hyperhomocysteinemia in Patients with Newly Diagnosed Primary Hypertension in Can Tho City, Vietnam.

Background: Elevated levels of blood total homocysteine is one of the cardiovascular risk factors in hypertensive patients. Objectives: Determine the prevalence of hyperhomocysteinemia and its associated factors in newly diagnosed primary hypertension patients. Materials and methods: A cross-sectional descriptive study on 105 patients with newly diagnosed primary hypertension at Can Tho University of Medicine and Pharmacy Hospital from May 2017 to May 2018. Total homocysteine levels and related factors were collected at the study time. Results: The mean plasma total homocysteine level was 16.24 ± 4.49 µmol/L. There were 78 patients with elevated plasma total homocysteine levels ≥15 µmol/L, accounting for 74.3% of all patients. Being elderly, gender, hypertension stage, and diabetes were factors associated with hyperhomocysteinemia (p < 0.05). Total homocysteine levels were positively correlated with SBP, DBP, and age with r(SBP) = 0.696, r(DBP) = 0.585, and r(age) = 0.286. Conclusion: Research on the subpopulation of Vietnamese people shows that hyperhomocysteinemia is common in patients with newly diagnosed primary hypertension, and high blood total homocysteine levels are often related to age, sex, hypertension stage, and diabetes.

Associations Between Elevated Plasma Total Homocysteine Level and Risk of Thromboangiitis Obliterans in a Chinese Population: A Matched Case-Control Study

Elevated plasma total homocysteine level is a risk factor for various vascular diseases; however, an association with risk of thromboangiitis obliterans (TAO) has not been defined. This study aims to assess whether elevated plasma total homocysteine level is associated with risk of TAO. We performed a matched case-control study including 64 patients with TAO and 256 controls. Multivariate logistic regression models were used to estimate the association between elevated plasma homocysteine level and the risk of TAO. Interaction and stratified analyses were conducted according to age, sex, smoking, alcohol consumption, and histories of chronic diseases. Patients with TAO versus controls had a higher mean plasma total homocysteine level (21.2±12.8μmol/L vs. 14.1±4.9μmol/L; P<0.01). The risk of TAO was 3.68-fold increased in participants with plasma total homocysteine level >15μmol/L (95% confidence interval [95% CI], 1.2-11.7). A 1μmol/L increase in plasma total homocysteine level was associated with 20% higher risk of TAO (odds ratio, 1.2; 95% CI, 1.1-1.3). Our findings suggest that the risk of TAO was significantly associated with elevated plasma total homocysteine level independently of other factors analyzed, including smoking. Studies on the use of homocysteine-lowering therapy to prevent TAO would allow testing causality of the latter association.

Cognitive and clinical outcomes of homocysteine‐lowering B‐vitamin treatment in mild cognitive impairment: a randomized controlled trial

Homocysteine is a risk factor for Alzheimer's disease. In the first report on the VITACOG trial, we showed that homocysteine-lowering treatment with B vitamins slows the rate of brain atrophy in mild cognitive impairment (MCI). Here we report the effect of B vitamins on cognitive and clinical decline (secondary outcomes) in the same study. This was a double-blind, single-centre study, which included participants with MCI, aged ≥ 70 y, randomly assigned to receive a daily dose of 0.8 mg folic acid, 0.5 mg vitamin B(12) and 20 mg vitamin B(6) (133 participants) or placebo (133 participants) for 2 y. Changes in cognitive or clinical function were analysed by generalized linear models or mixed-effects models. The mean plasma total homocysteine was 30% lower in those treated with B vitamins relative to placebo. B vitamins stabilized executive function (CLOX) relative to placebo (P = 0.015). There was significant benefit of B-vitamin treatment among participants with baseline homocysteine above the median (11.3 µmol/L) in global cognition (Mini Mental State Examination, P < 0.001), episodic memory (Hopkins Verbal Learning Test-delayed recall, P = 0.001) and semantic memory (category fluency, P = 0.037). Clinical benefit occurred in the B-vitamin group for those in the upper quartile of homocysteine at baseline in global clinical dementia rating score (P = 0.02) and IQCODE score (P = 0.01). In this small intervention trial, B vitamins appear to slow cognitive and clinical decline in people with MCI, in particular in those with elevated homocysteine. Further trials are needed to see if this treatment will slow or prevent conversion from MCI to dementia.

Plasma total homocysteine concentrations in a Turkish population sample

Objectives — The purpose of this study is to determine the reference of plasma total homocysteine levels from a Turkish population and to investigate the relationship of plasma total homocysteine levels with sex and age groups. Design and methods — Plasma total homocysteine levels were measured in 2257 Turkish individuals (1381 men and 876 women) aged 1-90 years. Plasma total homocysteine concentrations were determined using high performance liquid chromatography with fluorescence detector. Results — The mean plasma total homocysteine level was significantly higher in men (mean, 10.6 μmol/L) than in women (mean, 8.7 μmol/L), P < 0.001. The mean plasma total homocysteine levels for the 1-10, 11-20, 21-30, and 31-40, 41-50, 51-60, and 61-70, 71-80, 81-90 age groups, were 6.5, 9.6, 10.1, and 10.4, 10.5, 10.9, and 11.3, 12.7, 14.6 μmol/L in men and 7.1, 7.6, 7.5, and 7.8, 8.7, 9.4, and 10.3, 11.2, 13.3 μmol/L in women, respectively. Conclusions — These data indicate the significance of sex- and age-associated differences of plasma total homocysteine levels in Turkish subjects. Plasma total homocysteine levels were increasing with age and men were found to have higher levels than women, as is found in other populations.

Mortality and Cardiovascular Events in Patients Treated With Homocysteine-Lowering B Vitamins After Coronary Angiography

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.

Homocysteine and Diabetic Retinopathy

Homocysteine is an emerging risk factor for cardiovascular and nondiabetic ocular vaso-occlusive diseases. However, studies of the relationship between homocysteine and diabetic retinopathy have reported inconsistent results. The purpose of this study was to evaluate the relationship between plasma total homocysteine concentration and diabetic retinopathy. We assessed the homocysteine-retinopathy relationship in 168 men and women with type 2 diabetes in a community-based, cross-sectional study. We photodocumented diabetic retinopathy status and measured plasma total homocysteine concentration using a commercial fluorescence polarization immunoassay enzymatic kit. Data for selected clinical/demographic variables and established risk factors for diabetic retinopathy were obtained from fasting blood samples and an interviewer-assisted lifestyle questionnaire. A higher mean plasma total homocysteine concentration was observed in diabetic individuals with retinopathy than in those without retinopathy (11.5 mumol/l [95% CI 10.4-12.5] vs. 9.6 mumol/l [9.1-10.2], P = 0.001). Furthermore, the relationship between homocysteine and diabetic retinopathy was not explained by renal dysfunction and was independent of the other major risk factors for diabetic retinopathy (duration of diabetes, A1C, and systolic blood pressure) and determinants of higher homocysteine concentrations (age, sex, and red cell folate) (odds ratio 1.20 [95% CI 1.023-1.41], P = 0.024). Plasma total homocysteine concentration may be a useful biomarker and/or a novel risk factor for increased risk of diabetic retinopathy in people with type 2 diabetes.

Homocysteine, MTHFR C677 T, Vitamin B12, and Folate Levels in Thai Children With Ischemic Stroke: A Case-control Study

Hyperhomocysteinemia has been identified as a risk factor for venous and arterial thrombosis especially in adult populations. Twenty-eight patients with an initial diagnosis of ischemic stroke and 100 controls, aged <or=18 years, were enrolled in this study. The mean plasma total homocysteine (tHcy) levels in patients and controls were significantly different with values of 8.7+/-3.6 and 7.5+/-2.4 micromol/L, respectively (P=0.01). The plasma tHcy at the 95th percentile was 11.5 micromol/L and patients whose plasma tHcy was above the 95th percentile had an odds ratio of 8.2 (95% confidence interval 1.4-47.2, P=0.02) for developing ischemic stroke. The genetic and acquired factors that could have affected plasma tHcy levels were studied and no differences were found between patients and controls. Factors that were investigated were vitamin B12, red blood cell folate, and serum folate levels as well as methylenetetrahydrofolate reductase C677T polymorphism. It is of note, however, that subjects whose plasma tHcy was above the 95th percentile had significantly lower serum folate levels (P=0.02).

Plasma Total Homocysteine Level in Mothers of Children With Clubfoot

The pathogenesis of clubfoot is unknown despite numerous hypotheses. To clarify the relationship between the plasma total homocysteine level and congenital idiopathic clubfoot, blood samples from mothers of children with congenital idiopathic clubfoot (group 1) and mothers of children without congenital anomaly (group 2) were studied. Groups were the same for factors affecting the plasma total homocysteine level. Mean plasma total homocysteine level was 16.34+/-4.78 micromol/L in group 1 and 11.02+/-1.85 micromol/L in group 2, and there was significant statistical difference between the groups (P<0.05). Congenital idiopathic clubfoot showed a significant association with high plasma total homocysteine level. This study may be a step toward clarification of clubfoot pathogenesis.

Standardization of homocysteine on HPLC using DTT as reductant

Determination of plasma total homocysteine by high-pressure liquid chromatography (HPLC) usually requires reduction of protein bound or free homocysteine-disulphides into thiols by a reducing agent and the liberated thiols are then derivatized by a fluorescent marker. In this study we have standardized the HPLC method for homocysteine measurement using dithiothreitol (DTT) as reductant.The results of plasma total homocysteine values obtained by HPLC were compared with IMx method. The difference between the two means was statistically insignificant [P=0.616847 (two tail)] Linear regression analysis showed strong correlation between the two methods (r=0.983). Using this method we have analyzed 132 controls and 130 Coronary Heart Disease (CHD) patients for plasma total homocysteine, wherein, the mean plasma total homocysteine levels were 10.51±8.36 and 11.51±10.06 μmol/L respectively. Our research study suggests that DTT method is a simple and inexpensive assay for homocysteine determination in human plasma for research application.

Association between hyperhomocysteinemia and primary pulmonary hypertension

Study objective: This case-control study was conducted to test the hypothesis that fasting homocysteine levels are higher in PPH patients than in healthy controls. Design: Levels of plasma total homocysteine, serum folate, vitamin B-12, and serum creatinine in 18 consecutive patients with PPH were compared with data from 36 age- and sex-matched controls. Results: Eight of the 18 patients (44.4%) and three of the 36 controls (8.3%) had elevated plasma total homocysteine (tHcy) levels (⩾15μmol/l, odds ratio 8.8; 95% CI: 2.0–39.6; P=0.005). There was an inverse correlation between tHcy levels and creatinine clearance in patients with PPH (P=0.036). Conclusion: PPH patients are significantly more likely to have hyperhomocysteinemia, and higher mean plasma total homocysteine levels than in controls. Plasma total homocysteine may be an important factor in the pathogenesis of PPH.

Homocysteine, silent brain infarcts, and white matter lesions: The Rotterdam Scan Study.

Silent brain infarcts and white matter lesions are frequently seen on magnetic resonance imaging in healthy elderly people and both are associated with an increased risk of stroke and dementia. Plasma total homocysteine may be a potentially modifiable risk factor for stroke and dementia. We examined whether elevated total homocysteine levels are associated with silent brain infarcts and white matter lesions. The Rotterdam Scan Study is a population-based study of 1,077 people aged 60 to 90 years who had cerebral magnetic resonance imaging. The cross-sectional relation of total homocysteine with silent infarcts and white matter lesions was analyzed with adjustment for cardiovascular risk factors. The mean plasma total homocysteine level was 11.5 micromol/l (standard deviation 4.1). The risk of silent brain infarcts increased with increasing total homocysteine levels (odds ratio 1.24/standard deviation increase, 95% confidence interval 1.06-1.45). The severity of periventricular white matter lesions and extent of subcortical white matter lesions were also significantly associated with total homocysteine levels, even after excluding those with silent brain infarcts. The overall risk of having either a silent brain infarct or severe white matter lesions was strongly associated with total homocysteine levels (odds ratio 1.35/standard deviation increase, 95% confidence interval 1.16-1.58). We concluded that total homocysteine levels are associated with silent brain infarcts and white matter lesions independent of each other and of other cardiovascular risk factors.

Plasma homocysteine level in relation to folate and vitamin B6 status in apparently normal men.

The prevalence of subclinical deficiencies of folate and vitamin B6 in India is high and preliminary investigation showed higher mean plasma total homocysteine level in Indians compared with the values reported for western populations. The present study was carried out in 40 apparently normal men to examine the relationship between plasma total homocysteine level and folate and vitamin B6 status. The mean plasma homocysteine level was high and was inversely related to folate status as judged by red blood cells or plasma folate concentrations. There was no significant relationship between fasting homocysteine level and vitamin B6 status.

Moderate Hyperhomocyst(e)inemia Is Associated with the Presence of Coronary Artery Disease and the Severity of Coronary Atherosclerosis in Koreans

To examine whether moderate hyperhomocyst(e)inemia is associated with coronary artery disease and the number of diseased coronary vessels in Koreans, we investigated 201 patients with angiographically documented coronary artery disease and 187 healthy subjects without evidence of stroke and coronary artery disease. The mean plasma total homocysteine in patients was higher than in controls (10.3 μmol/L; 95% confidence interval, 7.0–13.6 vs. 8.9 μmol/L; 6.0–11.8) ( p=0.005). The prevalence of moderate hyperhomocyst(e)inemia, defined as the top 90th percentile in controls (13.2 μmol/L), was higher in patients than in controls (23.9% vs. 10.2%, p=0.001). Plasma homocyst(e)ine levels were not correlated to age, body mass index, levels of serum cholesterol, creatinine, and uric acid. Based on multiple logistic regression analyses with adjustment for total cholesterol, hypertension, smoking status, diabetes, age, and body mass index, the adjusted odds ratio of moderate hyperhomocyst(e)inemia for coronary artery disease was 1.53 (95% confidence interval: 1.39–1.65, p=0.0001). Moderate hyperhomocyst(e)inemia, diabetes mellitus, and old age were more prevalent in patients with triple-vessel disease than in single- or double-vessel disease ( p=0.02). Multiple logistic regression analysis revealed that moderate hyperhomocyst(e)inemia was a significant predictor of triple-vessel disease with odds ratio of 2.78 (95% confidence interval: 1.08–7.10, p=0.02). We conclude that moderate hyperhomocyst(e)inemia is an independent risk factor for coronary artery disease, and also related significantly to the presence of triple-vessel disease.

Plasma Homocysteine, Vitamin B6, Vitamin B12 and Folic Acid in End-Stage Renal Disease during Low-Dose Supplementation with Folic Acid

In order to see whether conventional low-dose folic acid supplement along with vitamin B₆ and B₁₂ reduces hyperhomocysteinemia in patients with ESRD, we compared the levels of homocysteine, vitamin B₆, B₁₂ and folic acid among 3 groups of patients: 44 ESRD patients on hemodialysis with replacement of folic acid, vitamin B₆, and B₁₂ (dialysis group); 27 chronic renal failure patients without vitamin replacement (predialysis group); and 17 hypertensive patients without vitamin replacement (control group). Mean plasma total homocysteine concentration was higher in the dialysis (15.5 ± 6.6 µmol/l) and the predialysis groups (15.7 ± 4.2 µmol/l) than in the control group (6.2 ± 1.5 µmol/l) (p < 0.001). However, there was no difference in homocysteine concentrations between the dialysis and predialysis groups. In the control and predialysis groups, the homocysteine concentration showed a reverse correlation with the concentrations of folic acid (r = 0.584, p = 0.014 for the control group; r = 0.431, p = 0.247 for the predialysis group) and vitamin B₁₂ (r = 0.485, p = 0.049 for the control group; r = –0.562, p = 0.023 for the predialysis group) but not with vitamin B₆. In conclusion, plasma folic acid concentrations were 3–4 times higher in the dialysis than in the predialysis group. But these levels of folic acid are not enough to reduce hyperhomocysteinemia in ESRD.

The relationship between plasma homocysteine and amino acid concentrations in patients with end-stage renal disease

Objective: Observe the relationship between homocysteine and other amino acids in patients with end-stage renal disease (ESRD). Design: A cross-sectional study of amino acids and homocysteine and comparison of the correlations between ESRD and control group. Setting: Nephrology unit of Soonchunhyang University hospital in Chunan, Korea. Participants: Forty-five ESRD patients and 30 control volunteers. Main outcome measures: Plasma amino acids and homocysteine. Results: Concentrations of asparate, proline and cysteine were higher and serine, tyrosine, valine, isoleuline, leucine, and lysine levels were lower in the ESRD group than in control group. The branched chain amino acids (BCAAs) and essential amino acid were lower in the ESRD group than in the control group, but there was no difference in non-essential amino acid and total amino acid between the two groups. The mean plasma total homocysteine concentrations were 6 ± 1 mmol/L in the control group and 14 ± 4 mmol/L in the ESRD group ( P < .001). In the ESRD group, homocysteine concentrations showed a direct correlation with the concentration of histidine ( R 2:.403, P<.001), valine ( R 2:.324, P<.01), leucine ( R 2:.400, P<.01), isoleucine ( R 2:.351, P<.005), cysteine ( R 2:.287, P<.001), methionine ( R 2:.256, P<.01), BCAA ( R 2:.50, P<.01), and essential amino acid ( R 2:.416, P<.01). In the control group, no correlation between the homocysteine and amino acid concentrations was found. Conclusions: Contrary to the control group, the homocysteine concentrations showed a direct correlation with the concentration of valine, leucine, isoleucine, methionine, and histidine levels in the ESRD group. Altered essential amino acid metabolism, specifically BCAAs and histidine, influence hyperhomocysteinemia in ESRD. Further study is needed to confirm this theory.