Plasma tHcy Levels Research Articles

Plasma homocysteine levels in patients with type 2 diabetes in a Mediterranean population: relation with nutritional and other factors

Hyperhomocysteinemia is a major and independent risk factor for atherothrombotic vascular disease. It may be promoted by genetic factors, nutritional deficiencies of the vitamin cofactors required for homocysteine metabolism, and other modifiable factors. This cross-sectional study investigated the effect of dietary habits and lifestyle on plasma total homocysteine (tHcy) levels in patients with type 2 diabetes in a Mediterranean population. A total of 126 diabetic and 76 healthy subjects were interviewed using a food-frequency questionnaire. Information consisted of dietary and smoking habits, coffee and alcohol consumption and physical activity recording, during the month prior to enrollment. Measurements included blood pressure, body mass index (BMI), waist-to-hip ratio (WHR), plasma tHcy, folate, vitamin B12, lipids, HbA(1c), creatinine, uric acid, and glomerular filtration rate (GFR). Plasma tHcy levels were not different between diabetic and control subjects (11.49+/-3.68 vs 12.67+/-3.79 micromol/l respectively, P = 0.40). Diabetic subjects had significantly higher plasma folate levels and consumed more fish, fruit and vegetables, in comparison with controls. Controls consumed more red meat, coffee, and alcohol. Multivariate analysis in diabetic subjects, after controlling for age, sex, systolic blood pressure, duration of diabetes, GFR, plasma uric acid levels, and the amount of the weekly consumption of fruit and vegetables, demonstrated that age, GFR and the weekly amount of fruit and vegetable consumption were independently associated with plasma tHcy concentrations [regression coefficient (B) = 0.11, SE (B) = 0.03, P = 0.001, B = -0.07, SE (B) = 0.01, P < 0.0001, and B = -0.05, SE (B) = 0.02, P = 0.04, respectively]. The weekly amount of coffee, alcohol and red meat consumption, and physical activity level were not related with plasma tHcy levels in either study group. 1) Plasma tHcy levels were not different in the diabetic group as compared to the control group. 2) In patients with type 2 diabetes age, GFR and the consumption of fruit and vegetables were strong and independent determinants of plasma tHcy levels.

The relationships between plasma total homocysteine and selected atherosclerotic risk factors according to the C677T methylenetetrahydrofolate reductase gene in Japanese

Variation of plasma total homocysteine (tHcy) levels among individuals is modified by 5,10-methylenetetrahydrofolate reductase (MTHFR) genotypes and selected atherosclerotic risk factors. Cross-sectional study. Healthy Japanese men (n=213) and women (n=242) aged 40-69 years were examined. Serum uric acid, hemoglobin, hematocrit, serum creatinine, and men were independently significantly associated with plasma tHcy. The relationship between serum uric acid and plasma tHcy was the strongest in those with the mutant homozygote (VV), but the overall statistical test of interaction was not significant. Serum uric acid, hematocrit, hemoglobin, creatinine, and men were determinants of plasma tHcy levels. Further investigations are needed.

Efecto del ácido fólico, el ácido levofolínico y el ácido fólico más vitamina B 12 en los valores de homocisteína plasmática total en mujeres sanas en edad reproductiva

Objective A high plasma total homocysteine (tHcy) concentration is a risk factor for neural tube defects, recurrent spontaneous abortion, and abruptio placentae. Elevated plasma tHcy can be lowered by administration of pharmacological doses of folic and levofolinic acid. The present study was performed to compare the homocysteine-lowering potential of folic acid with and without vitamin B 12 and levofolinic acid supplementation in healthy young women. Subjects and methods In a randomized, controlled trial, 60 healthy non-pregnant women, aged 18-40years old, were randomly assigned to receive one of the following three treatments for 30 days: supplementation with 5 mg/day of folic acid (oral) (n = 20) or 5 mg/day of levofolinic acid (oral) (n = 20) or 400 mg folic acid plus 2 μg vitamin B 12 (oral) (n =20). All the women followed their normal diets. Venous blood samples were collected after the subjects had fasted overnight, beginning at the start of the 30-day intervention period (day 0) and on days 2, 5, 10, 30, 60 and 90 of intervention. Plasma tHcy levels were determined by fluorescence polarization immunoassay (coefficient of variation: 3.1%). Data are expressed as total value (mmol/l). The data were analyzed for statistical differences using the Kolmogorov, Student, Bonferroni and ANOVA tests. Results There were no significant differences among the three groups with respect to baseline concentrations of plasma tHcy. Plasma tHcy levels decreased during the 30-day intervention and persisted below basal values on days 60 and 90. The differences in decreases among groups were statistically significant. Levofolinic acid had a faster and stronger effect in reducing tHcy levels than the same doses of folic acid and folic acid plus vitamin B 12. Conclusions These results suggest that supplementation with 5 mg/day levofolinic acid has a faster and stronger effect in reducing tHcy levels than the same doses of folic acid and folic acid plus vitamin B 12. This difference was significant from the fifth day of supplementation.

Homocysteine as a risk factor for CVD mortality in men with other CVD risk factors: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study

Based on case-control and prospective studies elevated blood total homocysteine (tHcy) has been suggested to be an independent risk factor for cardiovascular diseases (CVD). The purpose of the study was to explore the joint effect of increased serum tHcy concentration and other risk factors on the risk of CVD mortality in middle-aged men without a history of heart disease or stroke. A prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. Eastern Finland. Subjects. A total of 802 men aged 46-64 years, examined in 1991-93. CVD mortality event. The mean serum tHcy concentration was 10.8 micromol L(-1) (SD 3.3). During the average follow-up time of 10.8 years 50 men experienced a CVD death. The hazard rate ratio for CVD mortality was 1.80 (95% confidence interval: 1.02-3.19) in men in the highest serum tHcy third versus lower thirds after adjustment for cardiovascular risk factors. Furthermore, elevated serum tHcy concentration appeared to increase the risk of CVD death in men who smoke or who have high circulating concentrations of serum total or LDL cholesterol, apo-B apolipoprotein or plasma fibrinogen. We conclude that homocysteine may increase the risk of CVD mortality in middle-aged men from Eastern Finland, and it may especially increase the risk when present with other risk factors for CVD.

Impact of Elevated Plasma Total Homocysteine Concentration on Coronary Atherosclerosis in Chinese Patients With Acute Myocardial Infarction Undergoing Primary Coronary Intervention

Elevated plasma total homocysteine (tHcy) has been considered to be a new risk factor for coronary atherosclerotic disease. However, the association has not been proven indisputably, and the strength of the relationship and the interaction of plasma tHcy with other conventional risk factors remain uncertain in the clinical setting of acute myocardial infarction (AMI). The aim of this study was to investigate whether an elevated plasma level of tHcy is an independent predictor of the late stage of coronary atherosclerotic lesions in Chinese patients with AMI, who are undergoing primary percutaneous coronary intervention (PCI). Plasma levels of tHcy were prospectively measured in 178 consecutive patients with ST-segment elevated AMI undergoing primary PCI. The plasma level of tHcy was also measured in 30 control subjects with normal coronary angiographic findings. The plasma level of tHcy was significantly higher in the patients with AMI than in control subjects (10.5 +/- 3.3 micromol/L versus 8.3 +/- 2.4 micromol/L, P = 0.0004). Multiple stepwise logistic regression analysis of the baseline characteristics demonstrated that smoking (P = 0.004) and creatinine level (P < 0.0001) were independent predictors of an elevated plasma level of tHcy. Moreover, an increased plasma level of tHcy (P = 0.003), female gender (P = 0.008), diabetes mellitus (P = 0.020), and the presence of previous myocardial infarction (P = 0.003) were independent predictors of the late stage of multivessel diffuse atherosclerosis (defined by > or = 2 epicardial vessels with moderate or severe diffuse atherosclerosis). In conclusion, this investigation supports the hypothesis that a raised homocysteine concentration is a strong risk factor for the late stage of diffuse coronary atherosclerosis in Chinese patients with AMI undergoing primary PCI. This result therefore raises the prospect of the need for major therapeutic research in Chinese patients.

Plasma total homocysteine level and its association with carotid intima-media thickness in obesity

Elevated plasma concentrations of total homocysteine (tHcy) and obesity are risk factors for cardiovascular disease. The relationship between hyperhomocysteinemia and obesity has not been totally elucidated. The first aim of the study was to investigate whether anthropometric measurements and insulin resistance contribute to the variation in homocysteine levels in obese adults. Our second aim was to determine if any relationship exists between the carotid intima-media thickness (IMT) and plasma tHcy levels in obese subjects without traditional cardiovascular risk factors. Fifty-five obese (15 male, 40 female) and 30 (11 male, 19 female) age- and sex-matched apparently healthy volunteers were included. Exclusion criteria were smoking, hypertension, diabetes, vitamin ingestion, hyperlipidemia, renal failure, liver disease, pregnancy, menopause and secondary obesity such as Cushing's syndrome, hypothyroidism. tHcy, folate, vitamin B12 levels, fasting insulin, glucose, total cholesterol, triglycerides, HDL, LDL particles, uric acid, creatinine and creatinine clearance were measured. Non-invasive ultrasound measurements of carotid IMT were performed. tHcy levels and carotid IMT were comparable between obese and non-obese subjects. Waist/hip ratio (WHR) was related to tHcy and carotid IMT. Hyperhomocysteinemic subjects (tHcy >19.2 micromol/l) had greater WHR than normo-homocysteinemic subjects. Both tHcy levels and carotid IMT were higher in male subjects both in obese and non-obese subjects. No association was observed between insulin resistance and tHcy and carotid IMT. Renal function and abdominal obesity were significant predictors of plasma tHcy levels. We concluded that, in obese subjects who are free from atherosclerosis and impaired renal function, plasma tHcy levels do not differ from healthy subjects. Plasma tHcy concentrations are not related to carotid IMT in obese subjects during the non-atherogenic stage. Although no significant difference was observed between insulin-resistant and insulin-sensitive subjects compared to the plasma tHcy levels, the relationship between tHcy levels and some components of the insulin resistance syndrome may support the opinion that tHcy may be considered a component of the insulin resistance syndrome.

Age and kidney function are the primary correlates of fasting plasma total homocysteine levels in non-diabetic and diabetic adults. Results from the 1999–2002 National Health and Nutrition Examination Survey

BackgroundPlasma total homocysteine (tHcy) is commonly elevated in persons with diabetes. This may be due to effects of insulin and/or glucose and/or metabolic control on the metabolism or plasma levels of tHcy. This study examined the effects of fasting plasma glucose status on fasting tHcy levels among adults without diabetes, and diabetes per se among adults with a self-report history of diabetes.MethodsAnalysis of data on adults (≥ 20y) who had fasted at least 8 hours, from the National Health and Nutrition Examination Survey (1999–2000 and 2001–2002). Subjects with no self-report history of diabetes were grouped according to fasting plasma glucose status as normal (< 100 mg/dL = NFG, n = 2,244), impaired (≥ 100 < 126 mg/dL = IFG, n = 1,108), or a provisional diagnosis of diabetes (≥ 126 mg/dL = DFG, n = 133). Subjects with a self-report history of diabetes (n = 275) were examined separately.ResultsFasting tHcy was higher (Ps < 0.01) among non-diabetic subjects with DFG and IFG, compared to NFG (median [95% confidence interval] = 8.6 [8.0–9.2], 8.3 [8.1–8.5], and 7.4 [7.3–7.5] μmol/L, respectively). Diabetic subjects had levels similar to non-diabetic subjects with DFG and IFG (8.3 [7.9–8.6] μmol/L). Age and estimated creatinine clearance were strong correlates of fasting tHcy among non-diabetic subjects (r = 0.38 to 0.44 and r = -0.35 to -0.46, respectively) and diabetic subjects (r = 0.41 and r = -0.46, respectively) (Ps < 0.001), while fasting glucose and glycohemoglobin (HbA1c) were weaker (but still significant) correlates of tHcy in non-diabetic and diabetic subjects. Fasting glucose status was not a significant independent predictor of fasting tHcy levels in non-diabetic subjects, and HbA1c was not a significant independent predictor of tHcy in diabetic subjects (Ps > 0.05).ConclusionFasting tHcy levels are elevated among non-diabetic adults with elevated fasting glucose levels, compared to persons with normal fasting glucose levels, and among diabetic adults. However, elevations in fasting tHcy appear to be mediated primarily by age and kidney function, and not by measures of glucose metabolism.

Hyper-homocysteinemia is Not a Main Feature of Juvenile Uncomplicated Type 1 Diabetes

Total plasma homocysteine (tHcy) was measured by high pressure liquid chromatography (HPLC) method in 28 patients (12 females and 16 males) at the onset of type 1 diabetes mellitus (T1DM), 4 females during diabetes ketoacidosis (DKA) and 154 (68 females and 86 males) during follow-up. Serum folate, pyridoxal 5' phosphate (PLP) and Vitamin B12 (Vit B12) were also measured. Plasma tHcy levels were not found significantly different in T1DM patients known to have diabetes (males 9.2 +/- 7.7 and females 7.0 +/- 2.8 micromol/l) and in those who were newly diagnosed (males 9.7 +/- 4.8 and females 7.16 +/- 2.8 micromol/l) than in healthy controls (males 8.7 +/- 3.5 and females 7.8 +/- 2.55 micromol/l). Only a significant difference for sex was observed in known diabetes (p = 0.0281). Serum folate, PLP and Vit B12 were normal (12.6 +/- 3.6 ng/ml, 20.11 +/- 0.8 ng/ml and 416.7 +/- 41.9 pg/ml) in all T1DM patients. Age significantly correlated with plasma tHcy. Only in 4 patients, studied during DKA, plasma tHcy was significantly lower (2.76 +/- 1.33 micromol/l, p < 0.001) than the healthy controls.

Plasma homocysteine and markers for oxidative stress and inflammation in patients with coronary artery disease – a prospective randomized study of vitamin supplementation

Elevated plasma levels of total homocysteine (tHcy) are associated with an increased risk of developing occlusive vascular diseases. To better illustrate the relationship between plasma tHcy concentration, oxidative stress, and inflammation in patients with coronary artery disease (CAD), we measured plasma 8-isoprostane-prostaglandin F 2 (Iso-P), plasma malondialdehyde (MDA), and several markers of inflammation. We also aimed to demonstrate the effects of vitamin supplementation on these markers. A total of 93 patients with ischemic heart disease were investigated. Of these, 34 had plasma tHcy < or =8 micromol/L, while 59 had plasma tHcy > or = 15.0 micromol/L. The 59 patients were randomized to open therapy with folic acid, 5 mg, pyridoxine, 40 mg, and cyancobalamin, 1 mg once daily for 3 months (n = 29) or to no vitamin treatment (n = 30). Blood samples were obtained from both groups before randomization and 3 months later. A sample was also obtained from the remaining 34 patients. Plasma Iso-P, serum amyloid A (S-AA), and plasma intercellular adhesion molecule-1 (ICAM-1) concentrations were higher in patients with high plasma tHcy levels than in patients with low to normal tHcy levels. Plasma levels of P-, L-, E-selectins, MDA, C-reactive protein (CRP), and orosomucoid did not differ between the groups. Vitamin therapy reduced plasma tHcy from 17.4 (15.3/20.1) to 9.2 (8.3/10.3) micromol/L (25th and 75th percentiles in parentheses) (p<0.0001). Plasma levels of Iso-P remained unchanged and, of all inflammatory markers, only the S-AA concentrations were slightly reduced by the vitamin treatment, from 5.3 (2.2/7.0) ng/L at baseline to 4.6 (2.1/6.9) ng/L (p<0.05) after 3 months of vitamin supplementation. Patients with CAD and high plasma tHcy levels had elevated plasma levels of Iso-P. The increase remained unaffected by plasma tHcy-lowering therapy, suggesting that homocysteine per se does not cause increased lipid peroxidation. Levels of plasma ICAM-1 and S-AA were increased in patients with high plasma tHcy, suggesting an association between homocysteinemia and low-grade inflammation.

Inverse association between plasma homocysteine, sulphonylurea exposure and physical activity: a community‐based sample of type 2 diabetes patients in the Skaraborg hypertension and diabetes project

This study aimed to investigate levels of Homocysteine (tHcy) and folate in a population-based sample of patients with type 2 diabetes. In particular, the study explored modifiable determinants such as treatment for diabetes, life style, glucose control and kidney function. In a community-based surveillance of patients with type 2 diabetes, 196 men and 191 women were consecutively identified in primary care and characterized by cardiovascular disease (CVD) risk factors focusing on components in the metabolic syndrome. For categorical associations plasma tHcy was dichotomized using the upper 10 percentiles of the distribution. Treatment with sulphonylurea was associated with lower serum levels of tHcy compared to those on diet alone. The association was confined to women [odds ratio 0.14; confidence interval 0.03-0.8] and remained significant when differences in factors related to the metabolic syndrome, life style and previous CVD were accounted for, but was lost when adjusted for HbA1c. There was an inverse dose-related association between physical activity and plasma levels of tHcy (men p = 0.006, women p = 0.034), and a positive association with serum levels of creatinine (men p = 0.004, women p < 0.001). The association with physical activity might be one contributing explanation for its well-known protective effect on cardiovascular disease. The over risk for vascular complications in diabetic patients with kidney disease may be partially explained by high levels of tHcy and should be further explored. Prospective studies are particularly needed on various treatment for type 2 diabetes and tHcy to explore possible implications for clinical procedures and for public health.

Fasting Plasma Total Homocysteine Levels and Mortality and Allograft Loss in Kidney Transplant Recipients

Homocysteine is implicated to be an atherogenic amino acid and has been associated with increased risk of adverse cardiovascular outcomes. The prognostic significance of plasma total homocysteine (tHcy) levels for mortality and allograft loss in kidney transplant recipients has not been established. A total of 733 kidney transplant recipients who were seen for a routine visit at this transplant clinic in 1996 to 1998 were studied prospectively. During that visit, clinical information was collected and blood was drawn for laboratory evaluation. Information on the previous transplant procedure and the organ donor was obtained from the Eurotransplant Foundation database. Patients were followed prospectively using the Austrian Dialysis and Transplant Registry. With the use of proportional-hazards regression, the independent relations of fasting plasma tHcy levels to the risk of death from any cause and kidney allograft loss were examined. During a median follow-up of 6.1 yr, 154 participants died and 260 kidney allografts were lost. After adjustment for several important risk factors, elevated tHcy levels (>/=12 micromol/L) were associated with 2.44 times the mortality risk of patients with normal tHcy levels (hazards ratio 2.44; 95% confidence interval 1.45 to 4.12; P < 0.001). Similarly, elevated tHcy levels were associated with 1.63 times increased risk of kidney allograft loss (hazards ratio 1.63; 95% confidence interval 1.09 to 2.44; P = 0.02). In this single-center sample, baseline fasting plasma tHcy levels were independently associated with the risk of death and kidney allograft loss. The clinical utility of homocysteine-lowering therapy, such as multivitamin therapy, to reduce the rates of these end points needs to be studied.

Plasma homocysteine, vitamin B12 and folate in Alzheimer's patients and healthy Arabs in Israel

High plasma homocysteine (tHcy) is a risk factor for cardiovascular disease and stroke and Alzheimer's disease (AD). An inverse relationship has been reported between tHcy and plasma B12 and folate levels. Seventy-nine AD patients and 156 controls from three Arab villages in northern Israel participated. Plasma tHcy, B12 and folate levels were determined. Data were analyzed using univariate statistical tests and logistical regression with confounders. tHcy was significantly higher in AD patients (20.6±8.7 μmol/l) than in controls (16.4±6.5 μmol/l) ( p=0.03) after correction for year of birth, gender and smoking status. Plasma B12 (322.9±136.0/350.5±175.3 pmol/l) and plasma folate (4.5±3.8/4.9±2.6 nmol/l) levels did not differ significantly between AD patients and controls. Subjects in the highest tHcy tertile or in the lowest B12 and folate tertiles did not have greater risk to develop AD. In this population residing in Arab villages in northern Israel, tHcy levels were significantly higher among AD patients than in controls. Plasma B12 and folate levels were lower among cases but were not significant. There was not a significant association between plasma tHcy, B12 and folate levels in controls or AD patients. High levels of tHcy may suggest the need for folate and vitamin B12 supplementation in this population.

Dimercaptosuccinic acid for the treatment of hyperhomocysteinemia in hemodialysis patients: A placebo-controlled, double-blind, randomized trial

Elevated total homocysteine (tHcy) levels may represent a potentially modifiable risk factor for cardiovascular disease in hemodialysis patients. Current therapies, including multivitamins, have been ineffective at normalizing homocysteine levels in this population; hence, new therapies are needed. There is increasing interest in the use of thiol pharmaceutical agents to displace homocysteine from albumin and improve its dialyzability. We designed a randomized, double-blind, placebo-controlled trial to determine the effect of prolonged administration of oral dimercaptosuccinic acid (DMSA) on plasma tHcy levels in vitamin-replete hemodialysis patients. Forty-four long-term stable dialysis patients were treated for a minimum of 4 weeks with a standard multivitamin, ensuring a vitamin-replete state, then matched on the basis of tHcy levels and randomly assigned as pairs to the administration of DMSA, 2.5 mg/kg/d, or identical placebo for 8 weeks. Multivitamins were continued for the duration of the trial. Thirty-eight subjects (including 16 pairs) completed the trial. All important determinants of homocysteine level were balanced, and the only significant baseline difference was weight (P = 0.02). At 8 weeks, by paired analysis, there was no statistically significant difference in tHcy levels between the placebo and DMSA groups, at 21.2 micromol/L (2.87 mg/L) and 22.6 micromol/L (3.06 mg/L), respectively (mean difference, -1.4; 95% confidence interval, -5.3 to 2.5; P = 0.45). The same was true for unpaired and multivariable analyses. This randomized placebo-controlled trial found that prolonged oral administration of the thiol DMSA had no impact on tHcy levels in hemodialysis patients. Additional strategies to test the homocysteine hypothesis in this population require investigation.

Hyperhomocysteinemia in relation to plasma free amino acids, biomarkers of inflammation and mortality in patients with chronic kidney disease starting dialysis therapy

Plasma levels of total homocysteine (tHcy) and free amino acids (AAs) are influenced by nutritional status in patients with chronic kidney disease (CKD), whereas the role of chronic inflammation is not clear. In a cross-sectional analysis, fasting levels of plasma tHcy, total cysteine (tCys), AA, serum albumin (Alb), and several inflammation markers, including C-reactive protein (CRP), were analyzed in a cohort of 250 patients with CKD starting renal replacement therapy. Patients were followed up during a 4-year period to assess overall mortality in relation to basal tHcy level. Ninety-three patients (37%) with signs of inflammation (CRP > or = 1 mg/dL) had significantly lower levels of tHcy, tCys, and serum Alb than 157 noninflamed patients. tHcy and tCys levels correlated positively with serum Alb levels and negatively with CRP levels (rho = -0.24; P < 0.0001; rho = -0.15; P < 0.05, respectively) and other inflammation markers. tHcy and tCys correlated significantly with levels of several AAs. The presence of both inflammation and malnutrition was associated with lower tHcy levels than when malnutrition was present without inflammation. Multivariate analysis showed that serum Alb, CRP, plasma folate, and vitamin B12 levels were independently associated with tHcy levels after adjustment for other variables. tHcy, but not tCys, level was significantly greater in survivors than nonsurvivors, and Kaplan-Meier analysis showed that greater tHcy level was associated with better survival. Plasma tHcy and tCys levels are interrelated to plasma AA levels and were lower in patients with inflammation. Thus, inflammation may contribute to the reverse association between tHcy level and mortality in patients with CKD starting renal replacement therapy.

A PROSPECTIVE STUDY OF FASTING PLASMA TOTAL-HOMOCYSTEINE LEVELS AND MORTALITY AND ALLOGRAFT LOSS IN KIDNEY TRANSPLANT RECIPIENTS

P323 Aims: Homocysteine is an artherogenic amino acid and has been associated with increased risk of adverse cardiovascular outcomes. The present study aims to establish the prognostic significance of plasma total homocysteine (tHcy) levels for mortality and allograft loss in kidney transplant recipients. Methods: We prospectively studied 733 kidney transplant recipients who were seen for a routine visit at our transplant clinic in 1996-1998. During that visit, clinical information was collected and blood was drawn for laboratory evaluation. Information on the previous transplant procedure and the organ donor was obtained from the Eurotransplant Foundation database. Patients were followed prospectively using the Austrian Dialysis and Transplant Registry. Using proportional-hazards regression, we examined the independent relations of fasting plasma tHcy levels to the risk of death from any cause, and kidney allograft loss. Results: During a median follow-up of 6.1 years, 154 participants died and 260 kidney allografts were lost. After adjustment for several important risk factors, elevated tHcy levels (≥12μmol/L) were associated with 2.46-times the mortality risk of patients with normal tHcy levels (HR=2.46; 95% CI: 1.46-4.15; P<0.001). Similarly, elevated tHcy levels were associated with 1.7-times increased risk of kidney allograft loss (HR=1.70; 95% CI: 1.14-2.55; P=0.009). Conclusions: In this single-center sample, fasting plasma total homocysteine levels independently predicted the risk of death and kidney allograft loss. The clinical utility of homocysteine lowering therapy, such as multivitamin therapy, to reduce the rates of these endpoints needs to be studied.

Plasma homocysteine levels in living kidney donors before and after uninephrectomy

An increased prevalence of hyperhomocysteinemia has been observed among patients with end-stage renal disease, and numerous studies have demonstrated that kidney function is one of the most important determinants of plasma total homocysteine (tHcy) concentration. In an effort to understand the mechanism of hyperhomocysteinemia in renal disease, we chose, as our model, living kidney donors who had undergone uninephrectomy. We studied 10 living kidney donors and measured fasting plasma tHcy, plasma creatinine, folate, vitamins B 12 and B 6, and high-sensitivity C-reactive protein (hsCRP) 24 hours before nephrectomy and 2 days, 6 weeks, and 6 months after nephrectomy compared to the values 24 hours before nephrectomy. Mean fasting tHcy and creatinine concentrations were significantly higher in donors 2 days, 6 weeks and 6 months after nephrectomy they were 24 hours before nephrectomy. Both the increases in tHcy levels 2 days after nephrectomy and subsequent decreases 6 weeks and 6 months after are paralleled by the changes in plasma creatinine values, although neither returned to its presurgery value. Decreases in tHcy are significantly correlated with decreases in creatinine values. The B vitamins were unchanged, and the hsCRP level was increased 2 days after surgery but had returned to the baseline level after 6 weeks. We conclude that tHcy and creatinine levels parallel each other after uninephrectomy and that the gradual decrease in tHcy is accounted for by hypertrophy of the remaining kidney. Our results, the first to be obtained from living kidney donors, support the hypothesis that renal metabolism of tHcy is the mechanism responsible for the correlation between renal function and plasma tHcy level.

Effect of supraphysiologic doses of testosterone on fasting plasma total homocysteine concentrations in men with Klinefelter's syndrome

Objective To examine the effect of supraphysiologic doses of testosterone (T) on plasma total homocysteine (tHcy) concentrations in patients with Klinefelter's syndrome (KS). Design Prospective clinical study. Setting University hospital. Patient(s) Thirty-two newly diagnosed male patients with KS, and 20 healthy, volunteer controls matched by age and body mass index. Intervention(s) Testosterone was administered IM every 2 weeks for 6 months. Initially, pretreatment fasting blood samples were collected after overnight fasting. Posttreatment blood samples were drawn 7 days after the last injection. Main outcome measure(s) Plasma total homocysteine. Result(s) The KS patients had lower tHcy levels than the controls. However, plasma fasting tHcy concentrations increased in a statistically significant manner after 6 months of treatment. As compared with the levels among controls, pretreatment levels of the serum creatinine, hemoglobin, and hematocrit were significantly lower, and increased in a statistically significant way following treatment. Posttreatment levels of total cholesterol were statistically significantly higher than the baseline. The pretreatment folate and cobalamin levels also were statistically significantly higher in patients when compared with controls, and decreased significantly after treatment. The linear regression analysis showed that only creatinine, cobalamin, and folate were independently associated with plasma tHcy levels in patients before and after treatment. Conclusion(s) The patients with KS showed lower tHcy concentrations than healthy, age-matched male controls. Testosterone treatment increased plasma tHcy levels.

Levodopa-associated increase of homocysteine levels and sural axonal neurodegeneration.

Levodopa metabolism via catechol O-methyltransferase increases levels of the neurotoxin homocysteine, which induces an axonal-accentuated degeneration in sensory peripheral nerves in vitro. To demonstrate associations among daily levodopa/dopa decarboxylase inhibitor intake, total homocysteine plasma (tHcy) levels, and electrophysiologic sural nerve conduction findings. We performed bilateral assessment of sensory nerve conduction velocity and sensory nerve action potentials and determined tHcy levels. Thirty-one levodopa-treated patients with Parkinson disease (PD) and 27 control subjects. Sensory nerve action potentials significantly (P<.001) differed between PD patients and controls. No differences between sensory nerve conduction velocities of PD patients and controls appeared. We found significant differences in sensory nerve action potentials be-tween PD patients with significantly elevated tHcy levels and controls (P<.001), PD patients with tHcy levels within the reference range and those with elevated levels (P =.001), and PD patients with tHcy levels levels within the reference range and and controls (P =.04). Our sensory nerve conduction velocity results showed no significant differences. There were significant associations between tHcy levels and sensory nerve action potentials (R = -0.52; P =.002) and and sensory nerve conduction velocity (R = -0.47; P =.008). Daily levodopa/dopa decarboxylase inhibitor intake was significantly related to tHcy levels (R = 0.43; P =.02). This electrophysiological sign of peripheral neuronal dysfunction may be circumstantial evidence suggesting that, to a certain extent, sensory nerve action potentials are a surrogate marker for the levodopa metabolism-induced elevation of homocysteine levels and the aggravation of the ongoing central neurodegenerative process.

Various forms of homocysteine and oxidative status in the plasma of ischemic-stroke patients as compared to healthy controls

Objectives: We compared various forms of plasma homocysteine (Hcy) including total Hcy (tHcy), free reduced Hcy (reHcy), free oxidized Hcy (oxHcy) and reHcy plus oxHcy between patients with acute/subacute-ischemic stroke and healthy controls. We also investigated whether the patients have increased oxidative stress. Design and methods: Using an in-tube derivatization method, we measured plasma levels of tHcy, reHcy and oxHcy in 55 ischemic-stroke patients (14 females and 41 males, median age 64) and 52 age-matched healthy subjects (15 females and 37 males, median age 60). We also measured plasma malondialdehyde (MDA, as lipid peroxidation marker) and oxygen-radical absorbance capacity (ORAC, as total antioxidant activity). Results: The plasma levels of reHcy and reHcy plus oxHcy and the ratio of reHcy to oxHcy were significantly higher in the patients than in the age-matched controls, whereas tHcy and oxHcy levels were not significantly different. The patients had a significantly higher level of MDA but a lower value of ORAC than that of controls. A significantly positive correlation was found in the levels of reHcy vs. MDA ( r = 0.19, P < 0.03), whereas significant negative correlations were found for reHcy vs. ORAC ( r = −0.30, P < 0.001) and free Hcy vs. ORAC ( r = −0.30, P < 0.001). Conclusions: reHcy and reHcy plus oxHcy Hcy, rather than tHcy, are significantly elevated in patients with acute/subacute ischemic stroke. The elevated reHcy along with elevated MDA level and lowered ORAC value in the plasma of the stroke patients indicates an imbalance of antioxidant–prooxidant status in acute ischemic stroke.

Hyperhomocysteinemia: A Risk Factor for Retinal Vein Occlusion

Purpose: The aim of the study was to investigate the plasma homocysteine levels in patients with retinal vein occlusion (RVO) in order to reveal whether hyperhomocysteinemia was a risk factor for RVO. Methods: Thirty-three consecutive patients diagnosed to have RVO of any type and 25 age- and sex-matched controls without RVO were included in this prospective case-control study. Data regarding age, sex, history of hypertension, diabetes mellitus, other vascular events, glaucoma, medications and smoking habits were obtained from all subjects. Several laboratory tests relating to vascular disease including cholesterol, triglyceride and hematocrit were checked. The plasma total homocysteine (tHcy) level was measured by high-performance liquid chromatography (normal range: 5–15 µmol/l). Plasma folate, vitamin B₁₂ and creatinine levels were also studied since these vitamins and impairment of renal function might affect plasma tHcy values. Results: Patients with RVO had a significantly higher tHcy level (median: 11.7 µmol/l, range: 7.2–25 µmol/l) compared to controls (median: 10.3 µmol/l, range: 6.7–13.4 µmol/l; p = 0.005). Nine of 33 patients with RVO (27.3%) had an elevated plasma tHcy level, whereas none of the controls had an abnormal tHcy value (p = 0.004). Plasma folate, vitamin B₁₂ and creatinine levels were comparable between the two groups (p > 0.05). Conclusions: The present study suggests an association between hyperhomocysteinemia and RVO. Further controlled studies with a large number of cases are needed to investigate the exact role of hyperhomocysteinemia in RVO.