Association Of Hyperhomocysteinemia Research Articles

Association of hyperhomocysteinemia and chronic kidney disease in the general population: a systematic review and meta-analysis

BackgroundIncreasing evidence shows that an elevated homocysteine(Hcy) level is associated with an increased risk of chronic kidney disease (CKD). This study systematically evaluated the correlation between homocysteine level and the incidence of CKD reported in cohort and cross-sectional studies.MethodsWe searched electronic databases and reference lists for relevant articles. 4 cohort studies and 7 cross-sectional studies including 79,416 patients were analyzed in a meta-analysis. Hyperhomocysteinemia was defined as a Hcy level > 15 µmol/L, which was the criterium used in previous studies. Meta-analyses were conducted of literature searches from online databases such as PubMed, Embase, Cochrane and Scopus. Computed pooled adjusted odds ratios with corresponding 95% confidence intervals (95% CI) were used to estimate the risk of new-onset CKD according to Hcy levels in the general population.ResultsPeople with high Hcy levels were more likely to suffer from CKD than people with normal Hcy levels (pooled OR, 2.09; 95% CI, 1.72–2.55). This positive relationship persisted across different study types such as cohort studies (summary OR, 2.2; 95% CI, 1.55–3.13) and cross-sectional studies (summary OR, 2.07; 95% CI, 1.63–2.63).ConclusionsPeople with hyperhomocysteinemia have a higher incidence of CKD, Hyperhomocysteinemia may also be an independent risk factor for CKD in the general population.

The association of hyperhomocysteinemia with acute post-operative complications following coronary artery bypass grafting.

Hyperhomocysteinemia is associated with an increased risk for cardiovascular diseases. The influence of hyperhomocysteinemia on post-operative events, after coronary artery bypass surgery graft, is less studied. This cross-sectional study aimed to determine if hyperhomocysteinemia was associated with post-operative complications in patients < 50 years who underwent off-pump coronary artery bypass graft for coronary artery disease. A set of major post-operative complications were considered as primary outcome measures. The independent effect of hyperhomocysteinemia and other risk factors in the incidence of post-operative complications was determined by multivariate analysis. The mean homocysteine levels among the study participants who had post-operative complications were significantly higher than those without post-operative complications (17.37 mmol/L vs. 12.84 mmol/L). On multivariate analysis, hyperhomocysteinemia, diabetes mellitus, and higher body mass index (> 25) were significant predictors of adverse events during the post-operative period. Hyperhomocysteinemia was a significant predictor of immediate post-operative adverse events after coronary artery bypass surgery graft. Necessary precautions and management strategies have to be evolved for these high-risk subsets.

A study on serum homocysteine and oxidized LDL as markers of cardiovascular risk in patients with overt hypothyroidism.

Hypothyroidism is the most common endocrine disorder worldwide. Hypothyroisim increases cardiovascular risk, thus the study focuses on the assessment of cardiovascular risk factors such as serum Homocysteine, serum Oxidized LDL and Lipid profile and their correlation with TSH levels. Timely evaluation of these risk predictors would help in reducing cardiovascular disease morbidity and mortality in hypothyroidism. This was a hospital based cross-sectional study consisting of Forty newly diagnosed patients with overt hypothyroidism in the age group of 20-60 years attending Medicine OPD were included as cases and Fifty healthy age and gender matched healthy controls participated as controls in the study. A written and informed consent to all the participants of both thegroups was taken after explaining the purpose and details of the study. The Thyroid profile was assessed by CLIA-based MAGLUMI- 1000 analyzer and Serum total cholesterol, triglycerides and high-density lipoproteins were analyzed in Fully automated clinical chemistry analyzer EM-200 by using commercially available kits. LDL was calculated indirectly using Friedwalds equation. Commercially available ELISA-based kits were used for analysis of serum Homocysteine and serum oxidized-LDL. Elevated levels of serum homocysteine (p<0.0001), Oxidized LDL (p<0.0001) were found in newly diagnosed overt hypothyroid patients as compared to controls whereas significant elevated levelsof TC, TG, LDL, andVLDL (p<0.0001) and decrease in HDLcholesterol (p<0.0001) were reported in newly diagnosed newly diagnosed overt hypothyroid patients. We concluded that the association of hyperhomocysteinemia and lipid abnormalities occurring in hypothyroidism may represent a dynamic atherogenic state and thyroid hormone failed to completely normalize Hcy levels. Thus, elevated plasma homocysteine levels may be an independent risk factor for the accelerated atherosclerosis seen in hypothyroidism. In addition, we found that the circulating ox-LDL levels were elevated in untreated hypothyroidism and they tend to be higher in thyroid dysfunction.

Association of Hyperhomocysteinaemia with Hyperglycaemia, Dyslipidaemia, Hypertension and Obesity

There is conflicting scientific data about the link between, high homocysteine (Hcy) levels in the general population, and obesity. This is a case-control study aimed to assess the role of hyperhomocysteinemia in obesity and its associated illnesses, including hypertension, dyslipidemia, and hyperglycemia in Gezira state, Sudan. Two hundred and eleven participants were included in the study, 140 were obese (117 females and 23 males) and 71 were normal weight control, the obese median age was 49.49 ± 12.2 years. The control group consisted of 71 individuals with an average age of 45.78 ± 17.67 years. Among those who were already known to be obese, 67 (47.9%) reported having type II diabetes mellitus, 71 (50.7%) reported having hypertension, and 35 (25%) were obese without having either diabetes or hypertension. Three mls of venous blood from each participant were collected in the morning after a 12 h overnight fasting in Lithium heparin containers then the plasma was separated and stored at -80°C for analysis. Serum Hcy and lipid profile were measured using the enzymatic method by Cobas C 411 analyzer. In comparison to obese non-hypertensive, the results showed that obese hypertensive with Hcy levels > 15 mol/L had a considerably increased risk (OR 1.12). When Hcy levels > 15 mol/L were compared to obese diabetics and obese non-diabetics, insignificant difference was shown (P: 0.345). Males had a higher likelihood of having hyperhomocysteinemia than females did (OR 1.2). Homocysteine, cholesterol triglyceride, LDL, and HDL mean values were compared between case and control groups using the independent sample t-test, and the results revealed statistically significant (P: <0.05). Relationships between hyperhomocysteinaemia and cholesterol, triglycerides, LDL, and HDL in the group of obese individuals were not statistically significant (P: 0.574, 0.265, 0.748, and 0.14), respectively. Obesity and Hcyconcentrations were shown to be substantially correlated. However, there was no statistically significant association between baseline plasma Hcy levels and hyperglycemia, hypertension, or dyslipidemia.

Study on Homocysteinemia as a Risk Factor of Ischemic Stroke

Despite recent advances, only two-third of all strokes can be attributed to known causal risk factors. Homocysteine (tHcy), a sulfur-containing amino acid, is now considered to be an important risk factor for vascular diseases, along with the established risk factors like hyperlipidemia, hypertension, diabetes mellitus, and smoking. Elevated homocysteine levels play a causal role in the pathogenesis of atherosclerosis, thromboembolism and vascular endothelial dysfunction with an increased incidence of ischemic stroke. This study aimed to find out the association of hyperhomocysteinemia with ischemic stroke. A total of 100 subjects were included in this study, 50 were ischemic stroke patients enrolled as case, and 50 were normal healthy individuals enrolled as control. Serum homocysteine level was measured in both case and control groups. The comparison was made in both groups regarding other common risk factors like diabetes mellitus, hypertension, smoking, dyslipidemia, family history, etc. Among 100 patients, 50 had ischemic stroke and 50 were healthy individuals. In this study, out of all patients, abnormal serum homocysteine level was found in 32% of cases and 12% of controls. The mean (±SD) serum homocysteine level was found 16.50±13.86 μmole/L in cases and 9.46±3.49 μmole /L in the control group. Significant (p&lt;0.05) difference was found between the case and the control. The incidence of hyperhomocysteinemia is higher in ischemic stroke cases than that in age-sex-matched healthy controls. In our study, serum homocysteine was high in both younger age group patients (16.65±14.55 μmole/L vs. 9.52±3.19 μmole/L) and older age group patients (16.33±9.87 vs. 9.35±3.97 μmole/L,) in case and control group respectively. Significant (p&lt;0.05) difference was found between the case and the control. Multiple logistic regression analysis showed that abnormal serum homocysteine is an independent risk factor of ischemic stroke. So we conclude that hyperhomocysteinemia is an important and independent risk factor for the development of ischemic stroke. Hypertension and smoking are important contributory to elevated serum homocysteine.&#x0D; TAJ 2021; 34: No-1: 33-39

Association of Hyperhomocysteinemia with Early Onset Atherosclerotic Peripheral Arterial Occlusive Diseases

Background: Homocysteine is increasingly recognized as an independent risk factor for vascular disease specially peripheral arterial occlusive diseases. In the present study, an attempt was made to find out the association between the raised fasting plasma total homocysteine level and early onset atherosclerotic peripheral arterial occlusive diseases (PAOD).&#x0D; Methods: In this prospective observational study a total of 50 study subjects were included. All patients were clinically and angiographically documented for atherosclerotic PAOD. All patients underwent surgical intervention as well as estimation of serum total homocysteine level. Arterial segment was sent for histopathological examination to find out whether atherosclerosis was present or not. Patients were divided into two groups- Group-1 included patients of 20-40 years of age and group-II included those of 41-60 years of age. The groups were compared to see association between elevated level of plasma homocysteine and atherosclerotic peripheral arterial occlusive diseases in elderly as well as in early age.&#x0D; Results: 41 (82%) patients were male and 9 (18%) patients were female. Serum homocysteine level was higher in group I than group II (71.4% vs. 40.9%). Besides, the level of mean serum homocysteine level was significantly (p=0.02) higher in group I than group II (21.18±9.53 vs. 17.24±8.92 μmol/L).&#x0D; Conclusion: In conclusion, this study suggests that serum homocysteine has an association with early onset atherosclerotic PAOD. Therefore, a raised serum homocysteine level can be used as an independent biochemical predictor of early onset atherosclerotic PAOD.&#x0D; Cardiovasc. j. 2021; 13(2): 120-127

Homocysteine and markers of endothelial dysfunction in multiple sclerosis

To identify hyperhomocysteinemia and to assess its possible association with the course and other markers of endothelial damage in multiple sclerosis. Analysis of blood serum for homocysteine, for the content of adhesion molecules sPECAM-1, matrix metalloproteinase 9, blood plasma test for von Willebrand factor antigen in patients with multiple sclerosis. The values of these indicators were analyzed depending on the course and activity of the demyelinating process, the severity of neurological disorders, as also depending on the therapy received. Hyperhomocysteinemia was found in more than half of patients with multiple sclerosis. A significantly higher homocysteine level was found in male patients, and hyperhomocysteinemia was associated with the activity of the process in patients with highly active multiple sclerosis. The results of the study suggest a possible association of hyperhomocysteinemia with high process activity and disease progression, as well as with mechanisms of neurodegeneration. Determination of homocysteine concentration may be one potential marker for predicting the course of the disease.

Association of Hyperhomocysteinemia with Acute Myocardial Infarction in Iraqi Patients.

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Association of Hyperhomocysteinemia and Adverse Postoperative Outcomes of on-Pump Primary Isolated Coronary Artery Bypass Grafting Surgery among Postmenopausal Women

Studies investigating the possible role of hyperhomocysteinemia (HHC) in increasing postoperative morbidity and mortality among postmenopausal women undergoing on-pump primary isolated coronary artery bypass grafting (CABG) surgery are sparse in the literature. The knowledge about the relationship of preoperative HHC and postoperative adverse cardiovascular events is not adequately covered. This study is initiated to ascertain the hypothesized higher prevalence of HHC in postmenopausal women with ischemic heart disease (IHD) scheduled for on-pump primary isolated CABG and tracing its association to the proposed adverse postoperative complications especially thromboembolic ones linked in the literature to HHC.

Association of Hyperhomocysteinemia with Acute Myocardial Infarction in Kurdish Patients

Cardiovascular disease (CVD) is the main cause of death worldwide. Among multiple cardiovascular risk factors, such as age, blood pressure, diabetes, smoking and hyperlipidemia, hyperhomocysteinemia has recently emerged to have an important role in increasing risk of CVD by impairing oxidative stress-induced endothelial dysfunction and inducing atherothrombosis. However, the association between high circulating level of homocysteine and increasing the risk of CVD in human remains controversial and has not been consistently observed. OBJECTIVES: The aim of this study is to evaluate the association between serum total homocysteine (tHcy) concentrations with increased risk of CAD in patients with acute myocardial infarction (MI) in Kurdish population. In addition, correlations of classical risk factors including hypertension, smoking, diabetes and hyperlipidemia with hyperhomocysteinemia in MI patients were studied. Its role in in development of CVD could be pivotal. METHODS: In a case-control study, a total of 74 patients (51 male; 23 female; aged 22-80 years) who had diagnosed with acute CAD on angiography were enrolled in this study and 74 gender and age matched non-CAD individuals were included as the control group. The serum tHcy level was measured by enzymatic immunoassay. Hyperhomocysteinemia (HHcy) was defined as Hcy>15 µmol/l. RESULTS: the mean ± standard deviation (SD) of serum total homocysteine (tHcy) level in acute myocardial infarction patients was 22.8 ± 1.30 µmol/l, which was significantly higher compared to that of control group being 15.1 ± 1.33 µmol/l (P < 0.001), indicating that a high homocysteine level may promote pathogenesis of atherosclerosis. 51 (68.9%) MI cases had hyperhomocysteinemia; of these 35 MI patients (47.3%) had mild hyperhomocysteinemia (15-30µmol/L), and 16 MI patients (21.6%) had moderate levels of hyperhomocysteinemia (30-100 µmol/L). No significant correlation between tHcy levels and MI risk factors such as hypertension, hyperlipidemia, and diabetes mellitus, was observed. The tHcy levels were significantly higher in smoker patients than in non-smokers. CONCLUSIONS: These findings confirm that in patients with acute myocardial infarction, elevated homocysteine levels are associated with development of MI independent of other risk factors. A strong association between elevated levels of serum tHcy in MI patients was observed in Kurdish population. This study concludes that Hcy is considered as a strong emerging cardiovascular risk factor for development of myocardial infarction. Moreover, the measurement of Homocysteine levels might act as a surrogate laboratory marker and as one of the effective ways to diagnose patients with myocardial infarction in hospitals.

An uncommon presentation of hyperhomocysteinemia and vitamin B12 deficiency: a case report

IntroductionCerebral venous thrombosis is relatively rare and characterized by a wide spectrum of clinical features. It is more common in young adults with women affected more than men. The diagnosis of cerebral venous thrombosis is easier nowadays due to easy access to advanced neuroimaging techniques. Abnormalities in thrombophilic profile are associated with enhanced risk of cerebral venous thrombosis. It has varied etiologies such as hypercoagulable states, infection, dehydration, pregnancy, and substance abuse. Hyperhomocysteinemia is found to be closely associated with an enhanced risk of cerebral venous thrombosis.Case presentationHere we report a case of cerebral venous thrombosis secondary to hyperhomocysteinemia caused by vitamin B12 deficiency in a 32-year-old Indo-Aryan man. A detailed coagulation workup led us to find the etiology of cerebral venous thrombosis in this patient who followed a strict vegetarian diet and had vitamin B12 deficiency leading to hyperhomocysteinemia.ConclusionThere are conflicting reports in the literature about the association of hyperhomocysteinemia, B12 deficiency, and cerebral venous thrombosis but some reports point to a significant association. We conclude that further studies with a large sample size are required to analyze the effect of hyperhomocysteinemia and low vitamin B12 on the risk of cerebral venous thrombosis.

Association of hyperhomocysteinemia with genetic variants in key enzymes of homocysteine metabolism and methotrexate toxicity in rheumatoid arthritis patients.

The study investigated the association between plasma homocysteine, folate and vitamin B12 with 5,10 methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), thymidylate synthase (TYMS 2R→3R) and methionine synthase (MTR A2756G) polymorphisms and methotrexate (MTX) treatment and toxicity in Tunisian Rheumatoid arthritis (RA) patients. A total of 185 patients with RA were included. Homocysteine(Hcy) was assessed by fluorescence polarization immunoassay, and folate and vitamin B12 were measured by chemiluminescence immunoassays. The genetic polymorphisms were analyzed by PCR or PCR-RFLP. Hyperhomocysteinemia (HHC) was considered for Hcy > 15µmol/L. MTHFR C677T polymorphism was associated with HHC in RA patients (multi-adjusted OR, 95% CI 2.18, [1.07-4.57]; p = 0.031). No association was detected with the remaining polymorphisms. Plasma Hcy, folate, and vitamin B12 did not differ according to each polymorphism, or with MTX treatment or toxicity. However, HHC was more prevalent in patients with than those without MTX toxicity (32.7 vs. 16.7%; p = 0.035). The MTHFR 677TT genotype is an independent risk factor for HHC in Tunisians RA patients. HHC could be a useful marker of MTX toxicity in RA patients.

Neuro-fuzzy model of homocysteine metabolism.

In view of well-documented association of hyperhomocysteinaemia with a wide spectrum of diseases and higher incidence of vitamin deficiencies in Indians, we proposed a mathematical model to forecast the role of demographic and genetic variables in influencing homocysteinemetabolism and investigated the influence of life style modulations in controlling homocysteine levels. Total plasma homocysteine levels were measured in fasting samples using reverse phase HPLC. Multiple linear regression (MLR) and neuro-fuzzy models were developed. The MLR model explained 64% variability in homocysteine, while the neurofuzzy model showed higher accuracy in predicting homocysteine with a mean absolute error of 0.00002 μmol/L. Methylene tetrahydrofolate reductase (MTHFR) C677T, 5-methyltetrahydrofolate homocysteine methyltransferase (MTR) A2756G and 5- methyltetrahydrofolate homocysteine methyltransferase reductase (MTRR) A66G were shown to be positively associatiated with homocysteine, while nonvegetarian diet, serine hydroxymethyltransferase 1 (SHMT1) C1420T and TYMS 5'-UTR 28 bp tandem repeat exhibited negative association with homocysteine. The protective role of SHMT1 C1420T was attributed to more H-bonding interactions in the mutant modelled compared to the wild type, as shown through in silico analysis. To conclude, polymorphisms in genes regulating remethylation of homocysteine strongly influence homocysteine levels. The restoration of one-carbon homeostasis by SHMT1 C1420T or increased flux of folate towards remethylation due to TYMS 5'-UTR 28 bp tandem repeat or nonvegetarian diet can lower homocysteine levels.

Association of Hyperhomocysteinemia with Stroke Recurrence after Initial Stroke

Homocysteine (Hcy) is closely associated with stroke. Despite the fact that Hcy has consistently been shown to predict development of recurrent stroke, prior studies on the association of Hcy and stroke subtypes have been inconclusive. Data from the Ege Stroke Registry were examined and 5-year follow-up data were analyzed. Multivariate survival analyses were undertaken using Cox proportional hazards models to determine the prognostic value of Hcy in different ischemic stroke subtypes. Of the 9522 patients with stroke, 307 (27%) with hyperhomocysteinemia (hHcy) had recurrent stroke. Univariate Cox regression model showed that hHcy group was associated with recurrent stroke (crude hazard ratio [HR] 1.16; 95% CI 1.02-1.30). But there was no such association in multivariate regression models (adjusted HR 1.11; 95% CI .97-1.26). hHcy was not associated with any ischemic stroke subtypes at 5 years. Univariate Cox regression model showed that hHcy group was associated with overall cardiovascular events (crude HR 1.44; 95% CI 1.32-1.57). However, this association no longer existed in multivariate regression models (adjusted HR 1.01; 95% CI .93-1.12). Higher plasma Hcy group was significantly associated with higher mortality compared with normal plasma Hcy group (OR 1.83; 95% CI .45-2.32). Our results showed that elevated Hcy is not associated independently with stroke recurrence and overall cardiovascular events in patients with ischemic stroke. There was no association between the hHcy and stroke recurrence in the stroke subtypes within 5 years.

Lipid profile and levels of homocysteine and total antioxidant capacity in plasma of rats with experimental thyroid disorders

This study focuses on the relationship between serum levels of cholesterol and homocysteine with that of total antioxidant capacity in rats with thyroid dysfunction.Adult male Wistar rats were divided into three groups, a control (euthyroid), hypothyroidism and hyperthyroidism, each of them containing ten rats. Hypothyroidism was induced by administration of 0.1% aminotriazole in drinking water for 3weeks. Hyperthyroidism was induced by chronic subcutaneous injection of l-thyroxine (100μg/day, dissolved in 200μL saline solution/100g body weight) for 3weeks. The control and hypothyroid groups were injected subcutaneously with the same volume of saline solution.Results showed that hyperthyroidism is characterized by reduced serum thyroid stimulating hormone (TSH) levels despite increased free thyroxine (FT4) and free triiodothyronine (FT3) levels.Significant (p<0.05) elevation in serum levels of total homocysteine (t-Hcy) is reflected by a decrease in serum total antioxidant capacity (TAC) production in hypothyroidism comparing to control.There was a significant (p<0.05) elevation in serum levels of lipid profile (cholesterol, triglyceride and LDL) in hypothyroidism. Significant (p<0.05) reduction occurred in the levels of cholesterol and triglyceride in hyperthyroidism. The association of hyperhomocysteinemia and lipid abnormalities occurring in hypothyroidism may represent a dynamic atherogenic state.

Study on association of serum homocysteine with coronary heart disease in rural population

Background: CAD is the major cause of death. Many factors are responsible for causing CAD, but in 5 to 10 percent of CAD patients have none of the known risk factors. Risk factor modification is an integral part of the management of patients who have or are at risk for cardiovascular disease. Clinicians who care for patients with cardiovascular disease should be aware of new risk factors. Significant associations exist between established and new risk factors, and better understanding of new risk factors may shed light on the pathogenetic mechanisms of established risk factors. Objectives: To study the association of homocysteine in patients with coronary heart disease. Methods: This study was conducted in 50 patients of CAD and 50 people as a control group. All patients underwent a standard clinical examination and a blood draw for a lipid profile and total fasting serum homocysteine assay. Pearson chi-square test was used to assess the statistical significance. P value of less than 0.01 indicates highly significant and value of less than 0.05 indicates significant. Results: The cutoff value of homocysteine used in this study was 17micro mol/L. In case group 43 patients (86%) were showed raised homocysteine, and in control group 12 patients (24%) were showed raised homocysteine. And here the p value is <0.001 with the relative risk of 19.45. It shows raised homocysteine is statistically highly significant. Conclusions: The association of hyperhomocysteinemia with CHD was significant. Homocysteine values were higher in smokers and hypertensives.

Isolated abducens nerve palsy with hyperhomocysteinemia: Association and outcomes

Ischemic abducens nerve palsy usually presents as isolated cranial nerve palsy in the middle aged and elderly patients with known risk factors such as diabetes mellitus, hypertension, dyslipidemia, carotid artery disease, etc., In this report, we describe four patients with isolated abducens nerve palsy who presented with an acute onset diplopia whose detailed history and examination were suggestive of an ischemic etiology. Detailed systemic and laboratory evaluation revealed hyperhomocysteinemia as the only potential risk factor. To the best of our knowledge this is the first report of association of hyperhomocysteinemia and isolated abducens nerve palsy.

S-adenosylmethionine reduces the progress of the Alzheimer-like features induced by B-vitamin deficiency in mice

Methylation reactions linked to homocysteine in the one-carbon metabolism are increasingly elicited in Alzheimer's disease, although the association of hyperhomocysteinemia and of low B vitamin levels with the disease is still debated. We previously demonstrated that hyperhomocysteinemia and DNA hypomethylation induced by B vitamin deficiency are associated with PSEN1 and BACE1 overexpression and amyloid production. The present study is aimed at assessing S-adenosylmethionine effects in mice kept under a condition of B vitamin deficiency. To this end, TgCRND8 mice and wild-type littermates were assigned to control or B vitamin deficient diet, with or without S-adenosylmethionine supplementation. We found that S-adenosylmethionine reduced amyloid production, increased spatial memory in TgCRND8 mice and inhibited the upregulation of B vitamin deficiency-induced PSEN1 and BACE1 expression and Tau phosphorylation in TgCRND8 and wild-type mice. Furthermore, S-adenosylmethionine treatment reduced plaque spreading independently on B vitamin deficiency. These results strengthen our previous observations on the possible role of one-carbon metabolism in Alzheimer's disease, highlighting hyperhomocysteinemia-related mechanisms in dementia onset/progression and encourage further studies aimed at evaluating the use of S-adenosylmethionine as a potential candidate drug for the treatment of the disease.

Hyperhomocysteinemia and the methylene tetrahydrofolate reductase C677T mutation in splanchnic vein thrombosis

The role that hyperhomocysteinemia (HH) and the C677T mutation in 5,10-methylenetetrahydrofolate reductase (MTHFR) play in splanchnic vein thrombosis (SVT) remains unclear due to this unusual thrombotic location. To analyse the possible association of HH with the C677T mutation in the MTHFR gene in SVT. We determined homocysteine levels and the C677T MTHFR mutation, along with classical cardiovascular risk factors, in 48 patients with SVT (18 Budd-Chiari syndrome, 11 mesenteric vein thrombosis, 19 portal vein thrombosis) and 84 controls. In the univariate analysis, patients with SVT showed statistically higher homocysteine levels (P =0.044). After adjusting for total cholesterol, differences disappeared (P =0.256). However, no differences in homocysteine levels were observed when comparing the three SVT types (P =0.199), even after adjusting for age and total cholesterol (P =0.095). In addition, the prevalence of the TT genotype was no different when controls were compared with patients with SVT (P =0.253) or with SVT subtypes (P =0.885). No association was found between HH (>15 μm) and the TT genotype in cases (P =0.404), controls (P =0.178), or in the different SVT subtypes (P =0.495). Our results suggest that HH and the homozygous genotype in the MTHFR C677T mutation do not seem to play a role in SVT development.

Association of hyperhomocysteinemia with left ventricular dilatation and mass in human heart

Hyperhomocysteinemia is a risk factor for ischemic heart disease. Several other mechanisms apply also to dilative types of heart failure of various, non-ischemic etiologies. We hypothesized that hyperhomocysteinemia is associated with left ventricular (LV) dilatation and hypertrophy in dilative cardiomyopathy. Homocysteine was measured in 66 individuals with suspected cardiomyopathy. Cardiac magnetic resonance imaging was used to assess LV volume, mass, and wall stress. Hyperhomocysteinemia (> 12 micromol/L) was found in 45 patients (68%). LV mass was greater in these patients compared with individuals with normal homocysteine (83+/-27 vs. 67+/-19 g/m(2); p<0.02). Homocysteine was increased in patients with increased brain natriuretic peptide > or = 100 pg/mL (18.3+/-5.9 vs. 14.9+/-5.1 micromol/L; p=0.018). LV mass, LV end-diastolic and end-systolic volume (LVEDV, LVESV) were significantly increased in individuals in the upper quartile compared with the lower quartile (90+/-25 vs. 65+/-18 g/m(2), p=0.021; 114+/-50 vs. 71+/-23 mL/m(2), p=0.042; 76+/-51 vs. 36+/-22 mL/m(2), p=0.045). LV dilatation (LVEDV > or = 90 mL/m(2)) was more common in hyperhomocysteinemia (> 12 micromol/L, p=0.0166). Normalized LV mass was correlated with homocysteine (r=0.346, p=0.065). Homocysteine was not significantly correlated with LVEDV (r=0.229, p=0.065), LV end-diastolic wall stress (r=0.226, p=0.069) and LV ejection fraction. Hyperhomocysteinemia appears to be, at least in part, involved in a disproportional LV dilatation, where the ensuing hypertrophy is not sufficient to compensate for the increased wall stress. A potential mechanism is the hyperhomocysteinemia associated increase in oxidative stress that favors muscle fiber slippage.