Muscular contraction frequency does not affect plasma homocysteine concentration in response to energy expenditure- and intensity-matched acute exercise in sedentary males.

Acute exercise seems to increase total plasma homocysteine (tHcy); since this variable associated with cardiovascular risk, it is important to understand the determinants of its response to all types of exercise. The aim of this study was to examine the impact of cycling at 2 different rates of muscle contraction on the complete tHcy kinetics. Eight young sedentary males were required to complete 2 isocaloric (400 kcal) acute exercise trials at 50% peak oxygen uptake on separate occasions at 50 or 80 rpm. Blood samples were drawn at different points before (4 h before exercise and immediately before exercise), during (10, 20, 30, 45, and 60 min during exercise), and after exercise (immediately and 19 h after exercise). Dietary and lifestyle factors were controlled during the research. Maximum tHcy occurred during exercise for both conditions (50 rpm: 11.4 ± 2.7 µmol·L-1; 80 rpm: 10.8 ± 3.2 µmol·L-1). From this point onwards tHcy declined until the cessation of exercise and continued descending below pre-exercise values at 19 h postexercise (p < 0.05). No hyperhomocysteinemia were observed at any sampling point in both trials. In conclusion, the different muscular contraction frequency during exercise has no impact on tHcy during an acute bout of exercise in sedentary individuals, when at least 400 kcal are spent during exercise and the nutritional status for folate, B12, and B6 is adequate. This information is relevant to further inform healthy exercise prescription, not only in terms of duration and intensity of exercise, but also taking into account frequency of contraction.

Assessment of a possible link between hyperhomocysteinemia and hyperuricemia.

BACKGROUND/AIM: Hyperhomocysteinemia and hyperuricemia are both considered risk factors for coronary artery disease. However, the relationship between the 2 has not yet been thoroughly investigated. This study aimed to evaluate this relationship more closely. MATERIAL AND METHODS: This study is a retrospective cross-sectional analysis of data from a screening center in Israel assessing 16,477 subjects, within an age range of 20 to 80 years. RESULTS: The mean age of the study sample was 46 years, and 68% were males. Hyperuricemia was found in 24.9% and 14.6% of subjects with elevated and normal homocysteine serum levels, respectively (P < 0.001). A positive association was found between homocysteine serum levels and uric acid serum levels. Compared with subjects with normal homocysteine serum levels, those with hyperhomocysteinemia had an odds ratio (OR) for hyperuricemia of 1.7 (95% confidence interval [CI], 1.5-1.9) and 1.6 (95% CI, 1.1-2.5) for males and females, respectively. After multivariate adjustment for age, hypertension, body mass index, estimated glomerular filtration rate, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and thiazide use, the association remained significant in males (OR, 1.5; 95% CI, 1.3-1.7; P < 0.001) but not in females (OR, 0.9; 95% CI, 0.6-1.6; P = 0.82). CONCLUSIONS: This large cohort showed a significant association between hyperhomocysteinemia and hyperuricemia. Sex differences were observed. This study suggests that accelerated atherosclerosis may be a consequence of the combined effect of these 2 factors.

Early markers of occult megaloblastosis for low-cost detection of hyperhomocysteinemia in patients with ischaemic stroke: preventive approach for primary health care.

Recent studies have focussed on the association between elevated homocysteine levels with megaloblastic changes and thromboembolic events, but the relationship between occult megaloblastosis (with normal haemoglobin levels) and ischaemic stroke has not been widely explored. The objective of this study is to establish a simple and economical marker for the detection of occult megaloblastosis at the community health care level in developing countries. A hundred patients who met the inclusion criteria were studied. At the 5% level of significance, the levels of cobalamin and folate were significantly lower, while the number of hypersegmented neutrophils on the peripheral smear was higher in patients from Group A (70 patients with high homocysteine) compared with the patients in Group B (30 patients with normal homocysteine). Forty-five (64.2%) of the 70 patients in Group A showed hypersegmentation of neutrophils in the peripheral smear. The high cost and difficulty in performing the vitamin assays limit their use as early markers of megaloblastosis. Hence, we conclude that in developing countries, the detection of hypersegmented neutrophils can be used at the primary healthcare level for early diagnosis of occult megaloblastosis, so that early therapeutic interventions with vitamins can prevent attacks of hyperhomocysteinemia-induced ischaemic stroke.

Hyperhomocysteinemia and assessment of its associated factors in renal transplant recipients: a single-center study in northern Iran.

INTRODUCTION: Hyperhomocysteinemia (hyperHcy) is an important risk factor for atherosclerosis, which is currently a major cause of death in renal transplant patients (RTRs). The aim of this study was to determine the associated factors of hyperHcy in RTRs in northern Iran. METHODS: In 148 stable RTRs, total serum homocysteine (tHcy) level, folate, serum albumin and creatinine, creatinine clearance, lipid status, body mass index (BMI), and blood cyclosporine levels (C0 and C2) were determined. The mean doses of cyclosporine A (mg/kg/day) were recorded. RESULTS: In this analytic cross-sectional study the prevalence of hyperHcy was 70.3%. Hyperhomocysteinemia was defined as total serum homocysteine of 12 µmol/L or greater. The comparison of the group of 44 patients with tHcy level less than 12 and the group of 104 patients with tHcy level of 12 µmol/L or greater revealed that those subjects with hyperHcy were mostly younger, male, with lower BMI, history of glomerulonephritis, higher serum level of uric acid, and blood cyclosporine trough level (C0) and used higher doses of cyclosporine A. Significant correlation was found between tHcy level and recipients age, serum creatinine, BUN, folate concentrations, and creatinine clearance. However, multivariate analysis indicated that serum folate (P=0.01), vitamin B12 (P=0.05), creatinine (P=0.03), and BUN (P=0.05), and blood cyclosporine trough level (C0, P=0.005) were independently associated with tHcy levels. CONCLUSION: HyperHcy persists after successful kidney transplantation in the majority of RTRs. Serum creatinine, BUN, folate and vitamin B12, and blood cyclosporine trough level (C0) are independently associated with tHcy levels.

Noninvasive assessment of subclinical atherosclerosis in normotensive gravidae with gestational diabetes.

AIM: Carotid artery intima-media thickness (CIMT), hyperhomocysteinemia, microalbuminuria, and nitric oxide reflect subclinical atherosclerosis and predict the risk of future cardiovascular events. We aimed to evaluate the presence of subclinical atherosclerosis and endothelial dysfunction in normotensive patients with gestational diabetes mellitus (GDM) noninvasively. PATIENTS AND METHODS: We enrolled 41 normotensive patients with GDM and 44 healthy gravidae in the study. Serum homocysteine and nitric oxide levels, urinary albumin excretion (microalbuminuria), and CIMT were evaluated along with lipid parameters and anthropometric measurements. RESULTS: Patients with GDM had significantly higher levels of serum homocysteine, urinary albumin excretion, and increased CIMT (p < 0.001, p=0.005, and p < 0.001, respectively). Nitric oxide levels were significantly reduced in the patient group (p < 0.001). There was a significant difference between groups in terms of low-density lipoprotein (LDL) but not of high-density lipoprotein (HDL) and triglyceride levels. A significant correlation was observed between CIMT and serum LDL, HDL, homocysteine, nitric oxide levels, and urinary albumin excretion. Microalbuminuria was significantly correlated with serum homocysteine levels (p=0.03) but not with nitric oxide. CONCLUSION: Independent of elevated blood pressure, subclinical atherosclerosis and endothelial dysfunction exist in normotensive patients with GDM. Further studies with a large number of participants are required to clarify these data.

Assessment of cardiovascular risk in shift healthcare workers.

BACKGROUND: Shift work has been associated with an increased risk of cardiovascular disease (CVD); in particular, night work affects the circadian rhythm. DESIGN AND METHODS: The study examines the effectiveness of three screening methods and plasma hyperhomocysteinemia, an independent risk factor, in assessing the risk of CVD in 147 healthcare providers doing daytime or rotational shift work. The methods applied were: (i) the method proposed by the European Cardiovascular Indicators Surveillance Set (EUROCISS); (ii) the metabolic syndrome (MS) criteria of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATPIII) and (iii) the MS criteria of the International Diabetes Federation (IDF). RESULTS: EUROCISS was unable to distinguish between the CVD risk of daytime and rotational shift workers. Both the ATPIII and the IDF detected MS, which is strongly associated with CVD, but only the IDF evidenced a significantly greater prevalence of MS (P<0.05) among shift workers. Hyperhomocysteinemia was unable to discriminate the CVD risk between daytime and shift workers, as it was influenced by multiple confounding factors. CONCLUSIONS: The increased risk of CVD associated with shift work is related to the greater incidence of MS among these workers. In our study a high prevalence of MS was detected only with the IDF. The method is useful for CVD prevention and the promotion of health during any medical examination of shift workers.

Assessment of homocysteine, neopterin and nitric oxide levels in Behçet's disease.

BACKGROUND: Behçet's disease is a multisystemic immunoinflammatory disease with a wide variety of clinical manifestations, whereas recurrent aphthous stomatitis is a local oral disease. The aim of this study was to examine the distribution of homocysteine levels in patients with active Behçet's disease, possible association of homocysteine with nitric oxide and neopterin levels, and to characterize the differences between patients with Behçet's disease and those with recurrent aphthous stomatitis in terms of these parameters compared with healthy controls. METHODS: A total of 23 patients with active Behçet's disease, 25 patients with recurrent aphthous stomatitis as positive controls, and 21 healthy subjects were included in this study. Serum homocysteine and neopterin levels were measured flourimetrically by HPLC. Serum nitric oxide production was assayed by measuring total nitrite levels with Griess reagent. RESULTS: Significantly higher homocysteine (12.9+/-3.3 micromol/L) and lower nitric oxide (41.5+/-10.9 micromol/L) and neopterin (6.4+/-1.0 nmol/L) levels were observed in patients with Behçet's disease compared with healthy controls (10.7+/-2.0 micromol/L, 49.7+/-16.2 micromol/L, 8.7+/-2.2 nmol/L, respectively) (p<0.03 for neopterin, p<0.04 for homocysteine and nitric oxide). However, homocysteine, nitric oxide, biopterin and neopterin levels and the neopterin/biopterin ratio for recurrent aphthous stomatitis patients were not significantly different compared to healthy controls. A significant positive correlation was observed between serum homocysteine and serum neopterin/biopterin ratio in patients with Behçet's disease (r=0.975, p<0.005). CONCLUSIONS: In contrast to recurrent aphthous stomatitis, there is a higher prevalence of hyperhomocysteinemia in Behcet's disease. Homocysteine may have deleterious effects on the pathology of Behcet's disease by decreasing nitric oxide levels and interfering with the immune system.

An assessment of the potential value of elevated homocysteine in predicting alcohol-withdrawal seizures.

PURPOSE: Higher homocysteine levels were found in actively drinking patients with alcohol dependence. Recent studies have shown that high homocysteine levels are associated with alcohol-withdrawal seizures. The aim of the present study was to calculate the best predictive cutoff value of plasma homocysteine levels in actively drinking alcoholics (n = 88) with first-onset alcohol-withdrawal seizures. METHODS: The present study included 88 alcohol-dependent patients of whom 18 patients had a first-onset withdrawal seizure. All patients were active drinkers and had an established diagnosis of alcohol dependence, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Sensitivity and specificity were calculated by using every homocysteine plasma level found in the study population as cut-off value. A Bayes theorem was used to calculate positive (PPV) and negative (NPV) predictive values for all cutoff values used. RESULTS: The highest combined sensitivity and specificity was reached at a homocysteine plasma cutoff value of 23.9 microM. Positive predictive values ranged from 0.23 to 0.745; the maximum was reached at a homocysteine plasma level of 41.7 microM. Negative predictive values ranged from 0.50 to 0.935, with a maximum at a homocysteine plasma level of 15.8 microM. CONCLUSIONS: Homocysteine levels above this cutoff value on admission are a useful screening tool to identify actively drinking patients at higher risk of alcohol-withdrawal seizures. This pilot study gives further hints that biologic markers may be helpful to predict patients at risk for first-onset alcohol-withdrawal seizures.

Total homocysteine and cognition in a tri-ethnic cohort: the Northern Manhattan Study.

OBJECTIVE: Several studies implicate elevated homocysteine as a risk factor for dementia and cognitive decline, but most studies have involved subjects older than 55 years from homogeneous populations. The authors examined homocysteine and cognition in a tri-ethnic community sample 40 years and older. METHOD: The Northern Manhattan Study includes 3,298 stroke-free subjects. Of these 2,871 had baseline fasting total homocysteine (tHcy) levels and Mini-Mental State Examination (MMSE) scores available. The authors used multiple linear regression to examine the cross-sectional association between baseline tHcy levels and mean MMSE scores adjusting for sociodemographic and vascular risk factors. RESULTS: Homocysteine levels were related to age, renal function, and B12 deficiency. Those with B12 deficiency had tHcy levels five points higher (9.4 vs 14.4 nmol/L). Mean MMSE scores differed by age, sex, and race-ethnic group. Those with hypertension, diabetes, cardiac disease, and B12 deficiency had lower MMSE scores. In multivariate analyses, elevated tHcy was associated with lower mean MMSE scores for those older than 65 but not for those 40 to 64. Adjusting for B12 deficiency and sociodemographic factors the mean MMSE was 2.2 points lower for each unit increase in the log tHcy level (95% CI -3.6, -0.9). Adding vascular risk factors to the model did not attenuate this effect (mean MMSE -2.2 points; 95% CI -3.5, -0.9). CONCLUSIONS: Elevated homocysteine was independently associated with decreased cognition in subjects older than 65 in this tri-ethnic cohort, adjusting for sociodemographic and vascular risk factors.

The use of coagulation activation markers (soluble fibrin polymer, TpP, prothrombin fragment 1.2, thrombin-antithrombin, and D-dimer) in the assessment of hypercoagulability in patients with inherited and acquired prothrombotic disorders.

A total of 260 consecutive patients, referred for hypercoagulable assessment, was included in this study. Four coagulation activation markers were utilized to assess these patients [enzyme-linked immunosorbent assays for soluble fibrin polymer (TpP), prothrombin fragment 1.2, thrombin-antithrombin complex, and D-dimer]. The mean levels of the activation markers directly correlated with the number of hypercoagulable abnormalities. The percentage of patients with increased TpP levels for each group was lower than the other activation markers. The findings indicate that activation markers reflect the number of underlying thrombophilic abnormalities. Our data suggest that there is a utility in performing a panel of coagulation activation markers to assess the thrombotic risk. The measurement of soluble fibrin polymer may be more reflective of an impending vascular event.

Assessment of homocysteine as a cardiovascular risk factor in clinical practice.

Elevated plasma total homocysteine concentrations are a marker of vitamin deficiency and a risk factor for cardiovascular disease. It is possible that vitamin supplementation with folic acid and other B vitamins, which lower plasma homocysteine concentrations, may reduce the risk of cardiovascular disease. Large-scale clinical trials are currently underway to assess the homocysteine hypothesis of cardiovascular disease. Pending the outcome of such trials, measurement of plasma homocysteine concentrations in people at high risk of cardiovascular disease may help to identify patients who could benefit from more intensive treatment of classical cardiovascular risk factors. The introduction of immunoassays for homocysteine determination has made assessment of homocysteine status accessible to most routine hospital laboratories, and this review summarizes the evidence on why and how to assess homocysteine as a risk factor for cardiovascular disease in clinical practice.

Risk assessment of alcohol withdrawal seizures with a Kohonen feature map.

Recently, it has been suggested that alcohol-induced hyperhomocysteinaemia in patients suffering from chronic alcoholism might be a risk factor for alcohol withdrawal seizures. In the present follow-up study 12 patients with chronic alcoholism who suffered from withdrawal seizures had significantly higher levels of homocysteine (Hcy) on admission (71.43 +/- 25.84 mol/l) than patients (n = 37) who did not develop seizures (32.60 +/- 24.87 mol/l; U = 37.50, p = 0.0003). Using a logistic regression analysis, withdrawal seizures were best predicted by a high Hcy level on admission (p < 0.01; odds ratio 2.07). Based on these findings we developed an artificial neural network system (Kohonen feature map, KFM) for an improved prediction of the risk of alcohol withdrawal seizures. Forty-nine patients with chronic alcoholism (12 with alcohol withdrawal seizures and 37 without seizures) were randomized into a training set and a test set. Best results for sensitivity of the KFM was 83.3% (five of six seizure patients were predicted correctly) with a specificity of 94.4% (one false positive prediction of 19 patients). We conclude that in patients with alcohol-induced hyperhomocysteinaemia the KFM is a useful tool to predict alcohol withdrawal seizures.