The serum homocysteine level in patients with acute ischemic stroke (AIS) after thrombolysis and its relationship with clinical outcomes

SUMMARY OBJECTIVE The present study aims to investigate whether hyperhomocysteinemia (HHcy) affects the outcomes of the thrombolytic treatment for patients with AIS. METHODS A sample of 120 AIS patients were recruited and grouped according to their serum homocysteine (Hcy) levels. The National Institute of Health Stroke Scale (NIHSS) was obtained before treatment and 7 days after it to evaluate neurological outcomes; modified Rankin Scale (mRS) was obtained 12 weeks later to assess functional outcomes. Receiver operating characteristic curve (ROC) was used to demonstrate the relationship between serum Hcy level and the outcomes after tPA treatment. RESULTS The serum Hcy level of 120 patients was of 27.57±20.17μmol/L. The NIHSS scores of the patients in the low Hcy level group were remarkably lower compared to those in the high-level group (p<0.05), after 7 days of treatment. In addition, the mRS scores of the patients in the low Hcy level group, after 12 weeks, were remarkably lower compared to those in the high-level group (p<0.01). ROC demonstrated that the serum Hcy level is related to the clinical outcomes of thrombolytic treatment with moderate specificity (80.3%) and sensitivity (58.2%). CONCLUSION In conclusion, higher serum Hcy levels can indicate poorer clinical outcomes of thrombolytic treatment in patients with AIS.

RESUMO OBJETIVO O presente estudo tem por objetivo investigar se a hiperhomocisteinemia (HHcy) afeta os resultados do tratamento trombolítico em pacientes com AVCI agudo. METODOLOGIA Uma amostra de 120 pacientes AVCI agudo foi recrutada e agrupada de acordo com os níveis séricos de homocisteína (Hcy). Uma avaliação nos padrões do National Institute of Health Stroke Scale (NIHSS) foi obtida antes do tratamento e 7 dias após ele para avaliar desfechos neurológicos e a escala de Rankin modificada foi utilizada 12 semanas depois para avaliar os desfechos funcionais. A curva ROC (Receiver Operating Caracteristic) foi utilizada para demonstrar a relação entre os níveis séricos de Hcy e os desfechos após tratamento com t-PA. RESULTADOS Os níveis séricos de Hcy de 120 pacientes foi de 27,57±20,17μmol/L. Os escores NIHSS dos pacientes no grupo de baixo nível de Hcy foram notavelmente mais baixos em comparação àqueles do grupo de nível mais alto (p<0,05), após 7 dias de tratamento. Além disso, os escores mRS dos pacientes no grupo de baixo nível de Hcy, após 12 semanas, foram consideravelmente mais baixos em comparação com os do grupo de alto nível (p<0,01). A curva ROC demonstrou que o nível sérico de Hcy tem relação com os desfechos clínicos do tratamento trombolítico com especificidade moderada (80,3%) e sensibilidade (58,2%). CONCLUSÃO Podemos concluir então que níveis séricos mais altos de Hcy podem prever desfechos clínicos piores para o tratamento trombolítico em pacientes com AVCI agudo.

Hyperhomocysteinemia, a Biochemical Tool for Differentiating Ischemic and Nonischemic Central Retinal Vein Occlusion during the Early Acute Phase

PURPOSE: The purpose of the study was to differentiate ischemic central retinal vein occlusion (CRVO) from nonischemic CRVO during the early acute phase using plasma homocysteine as a biochemical marker. METHODS: Fasting plasma homocysteine, serum vitamin B12, and folate levels were measured in 108 consecutive unilateral elderly adult (age >50 years) ischemic CRVO patients in the absence of local and systemic disease and compared with a total of 144 age and sex matched nonischemic CRVO patients and 120 age and sex matched healthy control subjects. RESULTS: Homocysteine level was significantly increased in the patients with ischemic CRVO in comparison with nonischemic CRVO patients (p = 0.009) and also in comparison with control subjects (p 0.1). CONCLUSIONS: Hyperhomocysteinemia can be regarded as useful in differentiating nonischemic and ischemic CRVO during the early acute phase in absence of local and systemic disease in the elderly adult (age >50 years) population.

Comparison of homocysteinemia and MTHFR 677CT polymorphism with Framingham Coronary Heart Risk Score / Comparación de homocisteinemia y polimorfismo 677CT MTHFR con el Escore Framingham de Riesgo Coronario

Objective: The Framingham Coronary Heart Disease Risk Score is an important clinical tool. The aim of this cross-sectional study was to compare plasma homocysteine levels and polymorphism 677CT MTHFR with this score to determine the utility of these new biomarkers in clinical practice. Methods: Plasma homocysteine levels determined by chemiluminescence and polymorphism 677CT MTHFR, detected by PCR-RFLP, were compared with Framingham coronary risk score in a cross-sectional survey on 68 men and 165 women. Results: Coronary heart disease risk augmented with an increase in the quartile of plasma homocysteine. In the 2nd, 3rd and 4th quartile of plasma homocysteine, men showed significantly (P < 0.001) higher risk than women. For the highest quartile of plasma homocysteine, OR of high-risk (10-year risk ≥ 20%) compared with the lowest quartile was 17.45 (95% CI: 5.79-52.01). Frequencies of CT and TT genotype and T allele were not over-represented in the individuals with score ≥ 10%. The higher plasma homocysteine concentrations in individuals with score ≥ 10% with respect to those with low risk (P < 0.005 and P < 0.001) were not due to the presence of T allele. The T allele (CT + TT genotypes) of the MTHFR C677T polymorphism was not significantly associated with an increased risk of coronary disease (OR = 1.09, 95% CI = 0.50-2.39, P = 0.844). Conclusions: The present study demonstrated an association between plasma homocysteine levels and the severity of coronary heart disease estimated with the Framingham coronary risk score, and this association appeared to be independent on the genotype of MTHFR. We postulate that plasma homocysteine is effective enough, considered even in isolation.

Objetivo: La puntuación del riesgo coronario de Framingham es una importante herramienta clínica. El objetivo del presente estudio transversal fue comparar los niveles plasmáticos de homocisteína plasmática y el polimorfismo 677CT de la MTHFR con esta herramienta para determinar la utilidad de estos nuevos biomarcadores en la práctica clínica. Métodos: Los niveles de homocisteína plasmática determinados por quimioluminiscencia y el polimorfismo 677CT MTHFR por PCR-RFLP fueron comparados con la puntuación del riesgo coronario de Framingham en un estudio transversal sobre 68 hombres y 165 mujeres. Resultados: El riesgo de enfermedad coronaria aumentó con el incremento en los cuartiles de homocisteína plasmática. En el segundo, tercero y cuarto cuartil de homocisteína plasmática los hombres mostraron significativamente (p < 0.001) mayor riesgo que las mujeres. Para el cuartil más alto de homocisteína plasmática, la OR de riesgo alto (riesgo a 10 años ≥ 20%) comparado con el cuartil más bajo fue 17,45 (IC 95%: 5,79-52,01; p < 0.001). Las frecuencias de los genotipos CT y TT y del alelo T no estuvieron aumentados en los individuos con una puntuación ≥ 10%. Las mayores concentraciones de homocisteína plasmática en los individuos con una puntuación ≥ 10% respecto a los de bajo riesgo (p < 0.005 y p < 0.001) no se debieron a la presencia del alelo T. El alelo T (genotipos CT + TT) del polimorfismo MTHFR C677T no estuvo significativamente asociado con mayor riesgo de enfermedad coronaria (OR = 1.09, IC 95% = 0.50-2.39, p = 0.844). Conclusiones: El presente estudio mostró una asociación entre los niveles de homocisteína plasmática y la severidad de la enfermedad coronaria estimada con el algoritmo de puntuación de riesgo coronario de Framingham y esta asociación resultó ser independiente del genotipo de MTHFR. Postulamos que la homocisteína plasmática es lo suficientemente eficaz, estudiada incluso aisladamente.

Elevated Serum Homocysteine Levels Were Not Correlated with Serum Uric Acid Levels, but with Decreased Renal Function in Gouty Patients

Hyperhomocysteinemia is one of the important factors of the cardiovascular disease, and gout is well known to be associated with cardiovascular disease. There are a few reports on the serum homocysteine (Hcy) levels in patients with gout, however, the results showed discrepancies. In this study, we measured Hcy levels in patients with gout and examined factors associated with the levels of serum Hcy. Ninety-one male patients with gout and 97 age-matched healthy male controls were enrolled in the study. Serum uric acid levels were not significantly different between gout and healthy control groups. However, serum Hcy levels were significantly higher in patients with gout compared to controls (13.96+/-4.05 microM/L vs 12.67+/-3.52 microM/L, P=0.035). In gout group, patients with 1-2 stages of chronic kidney disease (CKD) had significantly lower serum Hcy than those with 3-5 stages of CKD (13.15+/-3.46 microM/L vs 17.45+/-4.68 microM/L, P<0.001). Multivariate linear analysis revealed an inverse association between serum Hcy and estimated glomerular filtration rate (eGFR) (beta=-0.107, P<0.001). In conclusion, serum Hcy was elevated in male patients with gout. Hyperhomocysteinemia was not correlated with serum uric acid, but it was inversely associated with impaired renal function.

Pulmonary thromboembolism due to severe hyperhomocysteinemia associated with a methyltetrahydrofolate reductase mutation

No abstract available.

Factores genéticos del sistema hemostático en pacientes jóvenes con infarto agudo del miocardio / Genetic factors of the hemostatic system in young patients with myocardial infarction

La enfermedad arterial coronaria (EAC) es la primera causa de muerte en todo el mundo y representa un problema de salud pública en México. El infarto agudo del miocardio (IAM) representa la principal complicación trombótica de la EAC. Aproximadamente 9 % de los nuevos casos está constituido por sujetos menores de 45 años. El IAM se produce por el desarrollo de un trombo en el sitio de la placa aterosclerosa, generando oclusión arterial súbita con isquemia y muerte celular. El IAM resulta de la interacción entre factores genéticos y ambientales. Existen diversos factores de riesgo modificables como la hipertensión arterial, la diabetes mellitus, el tabaquismo, la obesidad y la hipercolesterolemia asociados con el IAM. Sin embargo, numerosos pacientes con IAM no presentan factores de riesgo modificables. En la última década se han identificado variantes genéticas en las proteínas relacionadas con los sistemas de coagulación y fibrinólisis, receptores plaquetarios, disfunción endotelial, flujo sanguíneo anormal, metabolismo de la homocisteína, estrés oxidativo, los cuales se asocian a desarrollo del IAM. La identificación de los polimorfismos asociados a la enfermedad arterial coronaria permitirá desarrollar mejores estrategias de tratamiento e identificación de individuos con alto riesgo para EAC y medidas preventivas en etapas tempranas.

BACKGROUND: Coronary artery disease (CAD) is the first cause of death worldwide and represents a public health issue in our country. Acute myocardial infarction (AMI) represents the main thrombotic complication of CAD. Approximately 9% of the new events of MI occur in patients <45 years of age. DISCUSSION: AMI is produced by development of a thrombus at the site of an atherosclerotic plaque that initiates abrupt arterial occlusion, with ischemia and cell death. AMI results from the interaction of gene-environment factors. There are several modifiable factors such as hypertension, diabetes, smoking, obesity, and hypercholesterolemia associated with AMI. However, in a large number of patients with AMI, modifiable risk factors are not present. In the last decade, several genetic variants (polymorphisms) have been identified associated with AMI in genes related to coagulation proteins, fibrinolytic system, platelet receptors, homocysteine metabolism, endothelial dysfunction, abnormal blood flow and oxidative stress. CONCLUSIONS: Identifying the genes associated with CAD will allow us to develop more efficacious treatment strategies and will also help to identify at-risk subjects, thereby enabling the introduction of early preventive measures. Thus, many research efforts continue to address the identification of acquired and inherited risk factors of this complex disease.

Major Determinants of Serum Homocysteine Concentrations in a Korean Population

The objective of this study was to identify the factors that determine serum homocysteine concentrations in Korean population. In a community-based study, 871 participants completed detailed questionnaires and physical examination. We found that increased age, male sex, family history of stroke, deficiencies of serum folate and vitamin B12, and elevated serum creatinine significantly increased the risk of hyperhomocysteinemia. However, hormonal and behavioral factors (smoking, alcohol drinking, coffee consumption, and sedentary time) were not associated with the risk of hyperhomocysteinemia. The risk of hyperhomocysteinemia was steeply increased in subjects with two or more risk factors among four selected risk factors (deficiencies of serum folate and vitamin B12, elevated creatinine, and family history of stroke) compared to subjects who did not have any risk factors, especially subjects over the age of 65 yr (odds ratio [OR], 33.5; 95% confidence interval [CI], 3.71-302.0 in men; OR, 39.2; 95% CI, 7.95-193.2 in women). In conclusion, increased age, male sex, family history of stroke, deficiencies of serum folate and vitamin B12, and elevated serum creatinine are important determinants of serum homocysteine concentrations with interaction effects between these factors.

Influence of folic acid on plasma homocysteine levels & arterial endothelial function in patients with unstable angina.

Background & objectives: High plasma homocysteine (Hcy) levels are known to be associated with coronary artery disease, but the precise level associated with an increased risk is yet controversial. Whether the beneficial effects of folic acid on arterial endothelial function persist over longer periods is not known. This study was carried out to assess whether folic acid supplementation could produce improvements in Hcy levels and arterial endothelial function in the patients with unstable angina (UA) and hyperhomocysteinaemia. Methods: The plasma Hcy levels of 52 cases with UA and 30 control subjects were measured by using high-performance liquid chromatography (HPLC) with fluorescence detection, plasma folic acid and vitamin B12 levels were also measured. The patients with hyperhomocysteinaemia were treated with 5 mg of folic acid for 8 wk, and then rechecked the plasma levels of Hcy, folic acid and vitamin B12 at the end of 4th and 8th wk. Arterial endothelial function was measured as flow-mediated dilation of the brachial artery using high-resolution B-mode ultrasound in 22 cases with UA and hyperhomocysteinaemia before and after folic acid treatment. Results: The plasma Hcy level was significant higher in the patients with UA than in the controls (19.2 ± 4.9 vs 10.7 ± 5.3 μmol/l, P<0.01). The plasma levels of folic acid and vitamin B12 were significant lower in the patients with UA than in the controls. There were 22(42.3%) patients with hyperhomocysteinaemia in UA group. After 4 and 8 wk of administration of folic acid, the Hcy level reduced by 20.3 and 55.3 per cent in the UA patients with hyperhomocysteinaemia, respectively. Flow-mediated dilation also improved significantly, from 6.4 ± 1.9 to 9.0 ± 1.2 per cent (P<0.05) after 8 wk treatment with folic acid. Interpretation & conclusions: Plasma Hcy level was elevated in patients with UA. Folic acid can reduce the plasma Hcy levels and improve arterial endothelial function in the UA patients with hyperhomocysteinaemia.

A study of changes in homocysteine levels during normal pregnancy and pre-eclampsia.

To find out changes in homocysteine levels that occur during normal pregnancy and pregnancy with pre-eclamptic toxaemia and also to find out correlation between homocysteine concentration and preeclamptic toxaemia a study was carried out among 90 women of which 30 were control which included normotensive non-pregnant women and the study group I comprised 30 pregnant normotensive women and the study group II comprised 30 pregnant women with pre-eclamptic toxaemia. Serum homocysteine was measured in all subjects using fluorescence polarisation immuno-assay. Control group had highest mean homocysteine levels while the study group I had least mean homocysteine levels (p < 0.001). Levels were significantly higher in subjects with BP > 146/100 mm Hg as compared to subjects with BP >140/90 and <146/100 mm Hg (p=0.017). There was significant difference between study group I and II at same gestational age. Hyperhomocysteinaemia was observed in pre-eclamptic females, also it was found that homocysteine levels were directly correlated with severity of pre-eclampsia.

Vitamin B12 and homocysteine status in asymptomatic Indian toddlers.

Low serum vitamin B(12) (V B(12)) and hyperhomocysteinemia have been reported in asymptomatic Asian Indian men. We studied the prevalence of V B(12) deficiency and hyperhomocysteinemia in 51 asymptomatic toddlers, from Pune, India. V B(12) levels were low and total serum homocysteine was high in 14% and homocysteine levels were significantly higher in boys. Programming for cardiovascular risk in adulthood possibly starts at a very young age through the homocysteine axis.

Serum homocysteine in pre-eclampsia and eclampsia.

Pre-eclampsia and eclampsia are common obstetrical problem causing adverse effects on pregnancy outcome. Large bodies of evidences suggest that hyperhomocysteinemia is a causal factor of pre-eclampsia/eclampsia. This study designed to explore the association between hyperhomocysteinemia and pre-eclampsia/eclampsia, the knowledge of which expected to be used for prevention of pre-eclampsia and eclampsia. In a case-control study serum homocysteine was measured in 136 controls (healthy pregnant), 84 pre-eclamptic and 120 eclamptic pregnant women. Serum homocysteine in patients with pre-eclampsia (9.54 +/- 3.21 micromol/L) and eclampsia (10.57 +/- 3.39 micromol/L) found to be significantly increased compared to controls (6.86 +/- 2.47 micromol/L) (p < 0.001). Between pre-eclampsia and eclampsia, homocysteine found to be raised more in eclampsia compared to pre-eclampsia (p < 0.03). In conclusion, hyperhomocysteinemia is associated with pre-eclampsia as well as eclampsia, but in eclampsia the severity of homocysteine elevation is more compared to that in pre-eclampsia.

Clinical usefulness of a HPLC method for simultaneous quantitation of plasma homocysteine and cysteine.

OBJECTIVE: Homocysteine (Hcy) is a risk for vascular occlusion. It is metabolized via remethylation to methionine and transsulfuration to cysteine which has also been related to vascular occlusion. Simultaneous determination of Hcy and cysteine has additional clinical usefulness in providing a presumptive clue to the nature of hyperhomocysteinemia. MATERIAL AND METHOD: A manual HPLC method has been worked out for simultaneous determination of plasma Hcy and cysteine. Concentrations of Hcy were validated with the widely used automated Abbott AxSYM assay. Its usefulness was tested in 87 omnivores and 111 vegans. RESULTS: Excellent correlation between the values of Hcy was found between the manual HPLC method and the automated Abbott assay. The vegans had significantly higher levels of Hcy but lower levels of cysteine than the omnivores (mean +/- SD, micromol/L 23.6 +/- 18.0 vs. 8.8 +/- 2.1 p < 0.001, 225 +/- 30 vs. 245 +/- 34 p < 0.001, respectively). In contrast, the vegans had significantly lower levels of serum vitamin B12 and plasma vitamin B6 than the omnivores (median values 186 vs 565 pg/ml, p < 0.001; 37.4 vs. 47.4 nmol/L, p < 0.001 respectively). These findings indicate that the hyperhomocysteinemia in the vegans results from impairment of both remethylation and transsulfuration pathways of Hcy secondary to inadequacy of vitamins B12 and B6 respectively. Thus simultaneous determination of Hcy and cysteine is more useful than determination of only Hcy in that it provides a clue to the nature of hyperhomocysteinemia. CONCLUSION: The manual HPLC method and the Abbott assay gave comparable Hcy values, and thus can be used interchangeably. The HPLC method is economical, useful for hospitals with less demand for determination of Hcy, and capable of simultaneously determining cysteine which has implication in clinical practice.

Self-expandable nitinol stent placement in homocysteinemic porcine aorta

PURPOSE: To compare aortic intimal thickening of normal and hyperhomocysteinemic pigs (induced with a methionine-rich diet) following placement of a self-expanding nitinol stent. METHODS: Eighteen Macau pigs were used. They were older than eight weeks in age and had an average weight of 30 kg. Pigs were randomly divided into two groups. The first, Group C (control), was fed a regular diet, and the second group, Group M, was fed a methionine-rich diet for 30 days to induce hyperhomocysteinemia. The self-expandable nitinol stents were 25mm in length and 8 mm in diameter after expansion. Blood samples were collected to measure total cholesterol, triglycerides, HDL and homocysteine concentrations. All animals were subjected to angiography. Thirty days after the procedure, the animals were sacrificed, and the abdominal aorta was removed for histological and digital morphometry analysis. RESULTS: Under microscopic evaluation, the intima was significantly thicker in Group C than in Group M. When groups were compared by digital morphometric analysis, intimal thickening of the vessel wall was higher in Group C than in Group M. There was no significant change in total cholesterol, triglycerides or HDL concentrations in either group. In group C the levels of plasma homocysteine ranged from 14,40 to 16,73µmol/l; in Group M, plasma homocysteine levels ranged from 17.47 to 59.80 µmol/l after 30 days of a methionine-rich diet. CONCLUSION: Compared to normal pigs, less intimal hyperplasia was observed in the abdominal aortas of hyperhomocysteinemic pigs thirty days after the insertion of a self-expandable nitinol stent.

Hyperhomocysteinemia and central retinal vein occlusion in Iranian population

To evaluate total plasma homocysteine level during the acute phase of central retinal vein occlusion [CRVO] compared with a matched healthy group in Iranian population, and determine whether hyperhomocysteinemia is also a risk factor for CRVO. A study group contains 54 patients presenting with CRVO in recent one month, acute phase of the decease, was compared for fasting total plasma homocysteine level with a matched control group of 51 patients evaluated in the same clinic for a non retinal disease diagnosis. The mean total plasma homocysteine level was 14.76 +/- 7.67 micro mol/l in cases, and 11.42 +/- 3.74 micro mol/l in control subjects. It shows a significant difference [p=0.005] in mean plasma homocysteine level between the cases and control group. Odds ratio of CRVO for individuals with hyperhomocysteinemia was 2.88 [95% Cl=1.08-7.71 and p=0.03]. The overall multivanable-adjusted odds of CRVO in participants with plasma homocysteine level above 15 micro mol/l was 4.71 [95% Cl=1.46-15.19 and p=0.009] Hyperhomocysteinemia was not statistically different in each age group [<60 years: 27%. 61-70 years: 33.3%, 71-80 years: 31.6%, >81 years: 33.3%], Chi-square test, p=0.98]. Elevated total plasma homocysteine level is an independent risk factor for CRVO in Iranian population. In addition to an evaluation of all conventional cardiovascular risk factors, measurement of total homocysteine for evidence of hyperhomocysteinemia may be important in the initial investigation and management of patients with CRVO

Avaliação dos níveis séricos de homocisteína em transplantados renais com e sem hipercolesterolemia / Serum homocysteine levels in renal transplant recipients with and without hypercholesterolemia

FUNDAMENTO: A ocorrência de hiper-homocisteinemia parece ser freqüente após o transplante renal. Nenhum estudo até o momento avaliou o papel da homocisteína (Hcy) associada à dislipidemia no Brasil. OBJETIVO: Determinar a prevalência de hiper-homocisteinemia (Hcy sérica >15 mmol/l) em pacientes estáveis submetidos a transplante renal e avaliar o papel dos lipídios séricos e da função do enxerto nos níveis de Hcy sérica. MÉTODOS: Cento e cinco pacientes estáveis submetidos a transplante renal foram avaliados, levando-se em consideração idade, tempo pós-transplante, níveis séricos de colesterol, função do enxerto, proteinúria e uso de ciclosporina (analisados por regressão linear múltipla). A prevalência de hiper-homocisteinemia foi de 74,3 por cento. Os pacientes foram divididos em dois grupos: hipercolesterolêmicos (colesterol total > 200 mg/dl, colesterol LDL > 130 mg/dl) e normocolesterolêmicos. RESULTADOS: Os pacientes hipercolesterolêmicos eram mais velhos, tinham menor tempo pós-transplante, menor depuração de creatinina endógena, maior proteinúria e níveis séricos mais elevados de Hcy. Os pacientes com hiper-homocisteinemia tinham níveis séricos de triglicérides significativamente mais elevados e função do enxerto significativamente pior; além disso, seus níveis de colesterol LDL apresentaram tendência a ser mais elevados. Houve uma correlação positiva entre os níveis séricos de creatinina e de Hcy (r = 0,32; p = 0,01). A análise de regressão linear múltipla revelou que tanto a dislipidemia quanto a função renal afetam de forma independente os valores de Hcy. CONCLUSÃO: Observamos uma alta prevalência de hiper-homocisteinemia em pacientes submetidos a transplante renal, especialmente em hipercolesterolêmicos, sugerindo que uma pior função do enxerto pode influenciar negativamente os níveis séricos de Hcy e colesterol. Estudos futuros deverão investigar se esse perfil metabólico adverso está associado com maior mortalidade cardiovascular...

BACKGROUND: Hyperhomocysteinemia seems to be frequent after renal transplantation. No study so far has assessed the role of homocysteine (Hcy) associated with dyslipidemia in Brazil. OBJECTIVE: To determine the prevalence of hyperhomocysteinemia (serum Hcy >15 mmol/l) in stable renal transplant recipients and to evaluate the role of serum lipids and graft function in serum Hcy levels. METHODS: One hundred and five stable renal transplant recipients were evaluated, considering age, post-transplant time, cholesterol levels, graft function, proteinuria, and cyclosporine (analyzed using multiple linear regression). The prevalence of hyperhomocysteinemia was 74.3 percent. Patients were further divided into two groups, hyper (total cholesterol >200mg/dl, LDL-cholesterol >130mg/dl) and normocholesterolemic. RESULTS: Hypercholesterolemic recipients were older, had shorter post-transplant time, lower endogenous creatinine clearance, and higher proteinuria and Hcy serum levels. Patients with hyperhomocysteinemia had statistically significantly higher serum triglycerides and poorer graft function, and their LDL-cholesterol also tended to be higher. A positive correlation was found between serum creatinine and Hcy levels (r = 0.32, P = 0.01). Multiple regression analysis revealed that both dyslipidemia and renal function independently affect Hcy values. CONCLUSION: We observed a high prevalence of hyperhomocysteinemia in renal transplant recipients, especially in hypercholesterolemic, suggesting that worse graft function may influence serum Hcy and cholesterol levels negatively. Further studies should investigate if this adverse metabolic profile is associated with higher cardiovascular mortality in the long term.

Plasma homocysteine and ischemic stroke patients in Thailand.

BACKGROUND: Hyperhomocysteinemia was recently found to be a risk factor for stroke; however, the available data from Thailand is scarce. OBJECTIVE: To study plasma homocysteine levels in ischemic stroke and compare it with age-and sex-matched controls, and to identify the association of plasma homocysteine and subtype of stroke. MATERIAL AND METHOD: The authors studied plasma homocysteine levels of ischemic stroke patients with clinical signs and symptoms of stroke as confirmed by CT scan and compared them with control subjects who presented with other diseases and no clinical signs and symptoms of stroke between June 2000- May 2001 in Prasat Neurological institute. Fasting plasma homocysteine was measured by HPLC technique. Abnormal cut off point of plasma homocysteine was identified and associations of plasma homocysteine and stroke were studied by using logistic regression analyses. RESULTS: Two hundred and sixty-eight patients were recruited in the present study (132 controls and 136 ischemic stroke patients). The abnormal cut off point of plasma homocysteine was > 14 micromol/L. The authors found statically significant association of abnormal plasma homocysteine and stroke (p<0.001) with odds ratio of 4.277 (95%CI 2.551-7.171). After adjusting the confounding factor the authors found that high homocysteine was significantly associated with ischemic stroke (p<0.001) with odd ratio of 3.401 (95%CI 1.954-5.922). In the subgroup analyses of type of stroke and abnormal homocysteine, the authors demonstrated that abnormal homocysteine levels were more pronounced in the large vessel subtype than the small group. CONCLUSION: Abnormal homocysteine level is an independent risk factor of ischemic stroke and more correlated with large vessel subtype.

Homocysteine in cardiovascular disease: a culprit or an innocent bystander?

Whether hyperhomocysteinemia is a cardiovascular risk factor or is just an epiphenomenon is a subject of debate. More than 20 prospective and 30 retrospective studies on the topic have been published. Despite huge literature available, an unequivocal view has not been firmly established. Medical fraternity is still witnessing differing opinions regarding need to treat hyperhomocysteinemia. A medical practitioner needs to be well informed of developments and current opinion on this subject as it has a strong bearing on a major emerging public health problem of cardiovascular disease (CVD). This review presents the two views - for and against the acceptance of association between hyperhomocysteinemia and cardiovascular disease - and their basis. The two views are examined in the light of clinical, epidemiologic and genetic studies, reviews and meta-analyses available. Following conclusion was drawn from the exercise: The available evidence indicates that homocysteine is not an innocent bystander; it is an independent risk factor for CVD. The need for homocysteine-lowering therapy is however not yet unequivocally established. Physicians need to be vigilant of the updates on this much-debated topic thrusted on them time and again.

Presença de hiper-homocisteinemia em pacientes portadores de três fatores de risco para doença cardiovascular: hipertensão, tabagismo e histórico familiar / The presence of homocysteinemia in patients carrying three risk factors for cardiovascular diseases: hypertension, smoking habit and family history

A hiper-homocisteinemia é um fator de risco independente para desenvolvimento de doença cardiovascular e na presença de outros fatores de risco (FR) poderá acarretar em risco adicional para o surgimento do evento. Foram realizadas dosagens séricas de homocisteína e creatinina em 146 pacientes (51 homens e 95 mulheres) cadastrados no programa HIPERDIA/MS sendo todos portadores de três FR associados: hipertensão, tabagismo e histórico familiar para doença cardiovascular. A média geral foi de 14,48 µmol/L ± 5,98 (15,38 µmol/L ± 6,77 e 13,99 µmol/L ± 5,48, homens e mulheres respectivamente). A hiper-homocisteinemia esteve presente em 34,90% (39,20% e 32,60%, homens e mulheres respectivamente), de acordo com o intervalo de referência entre 5 - 15 µmol/L. Entretanto, segundo recomendações da DACH-LIGA Homocysteine, valores entre 12 - 30 µmol/L são considerados como moderada hiper-homocisteinemia. O estudo revelou que 60,30% (70,60% e 54,70%, homens e mulheres respectivamente) estavam acima de 12 µmol/L. Na avaliação do estudo, a dosagem de homocisteína sérica deve ser realizada em pacientes cadastrados no programa HIPERDIA/MS, pois além de hipertensos e/ou diabéticos, a presença de hiper-homocisteinemia pode ser um risco adicional para o desenvolvimento de doença cardiovascular.

Hiper-homocysteinemia is an independent risk factor in the development of cardiovascular diseases and in the presence of other risk factors (RF) may bring about an additional risk for the occurrence of the event. Serum dosages of homocysteine and creatinine in 146 patients (51 men and 95 women), registered at the HIPERDIA/MS Program, all presenting three associated RF's; hypertension, smoking habit and family history for cardiovascular diseases. The general average has been 14.48 µmol/L ± 5,98 (15,38 µmol/L ±6,77 and 13,99 µmol/L ± 5,48, for men and women respectively). Hiper-homocysteinemia had been present in 34.90% (39.20% and 32.60%, men and women, respectively), according to the reference interval between 5 - 15 µmol/L. Although, according to Homocysteine DACH-LIGA recommendations, values between 12 - 30 µmol/L are considered being a moderate hiper-homocysteinemia. The study has revealed that 60.30% (70.60% and 54.70%, men and women, respectively) had been above 12 µmol/L. In the evaluation of the study, the serum dosage of homocysteine has to be performed in patients registered at the HIPERDIA/MS Program for, besides being hypertense and/or diabetic, the presence of hiper-homocisteinemia may be an additional risk for the development of cardiovascular disease.

Homocistéina e metilenotetrahidrofolato redutase em indivíduos submetidos à angiografia coronariana / Homocysteine and methylenetetrahydrofolate reductase in subjects undergoing coronary angiography

OBJETIVO: Determinar os níveis plasmáticos de homocisteína e a incidência do polimorfismo C677T no gene da enzima metilenotetrahidrofolato redutase (MTHFR) em um grupo de indivíduos submetidos a angiografia coronariana, buscando estabelecer a possível correlação entre esses parâmetros e a gravidade da doença arterial coronariana (DAC), bem como investigar a correlação entre hiper-homocisteinemia e a presença do polimorfismo. MÉTODOS: Vinte indivíduos com ausência de ateromatose nas coronárias (controles), quatorze indivíduos apresentando ateromatose leve/moderada e vinte e nove indivíduos apresentando ateromatose grave foram avaliados. RESULTADOS: Para o parâmetro homocisteína foram observadas diferenças significativas entre as médias dos grupos controle e ateromatose grave (p < 0,001). Entre os demais grupos não foram observadas diferenças significativas. O grupo ateromatose grave apresentou uma freqüência de 62,0 por cento e 6,9 por cento para o polimorfismo C677T no gene da enzima MTHFR, em heterozigose e homozigose, respectivamente. Entretanto, não foi observada correlação entre a presença da mutação e hiper-homocisteinemia. Foi observada uma correlação positiva da ordem de 41,91 por cento (p < 0,001) entre hiper-homocisteinemia e a presença de DAC. CONCLUSÃO: O achado mais importante deste estudo foi a associação entre hiper-homocisteinemia e a presença de estenose coronariana superior a 70 por cento; entretanto, permanece a dúvida se o aumento da concentração plasmática de homocisteína constitui um fator determinante para o agravamento da lesão aterosclerótica nas coronárias ou se o mesmo é uma conseqüência desta lesão.

OBJECTIVE: To determine plasma homocysteine levels and the incidence of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism in a group of subjects who underwent coronary angiography, in an attempt to establish a correlation between these parameters and the severity of coronary artery disease (CAD), as well as investigate the correlation between hyperhomocysteinemia and the presence of polymorphism. METHODS: Twenty subjects with no coronary atheromatosis (controls), fourteen subjects with mild/moderate atheromatosis, and twenty-nine subjects with severe atheromatosis were evaluated. RESULTS: Significant differences were observed in mean homocysteine levels between the control and the severe atheromatosis groups (p < 0.001). No significant differences were observed among the other groups. The severe atheromatosis group showed rates of 62.0 percent and 6.9 percent for the C677T MTHFR gene polymorphism, in heterozygous and homozygous subjects, respectively. However, there was no correlation between the presence of mutation and hyperhomocysteinemia. A positive correlation of 41.91 percent (p < 0.001) was found between hyperhomocysteinemia and CAD. CONCLUSION: The most important finding of this study was the association between hyperhomocysteinemia and coronary stenosis > 70 percent; yet, whether elevated plasma homocysteine worsens atherosclerosis or is a consequence remains to be established.

Hyperhomocysteinaemia in renal allograft recipients: could methylenetetrahydrofolate reductase gene polymorphism be a determinant risk factor for chronic allograft dysfunction?

The elevated plasma homocysteine could adversely influence long-term renal graft survival by promoting vascular sclerosis in the kidney allograft. This could be mediated through endothelial dysfunction. A polymorphism C677T in the gene coding for the enzyme methylenetetrahydrofolate reductase [MTHFR] was identified. The aim of the present work was to study the influence of the C677T MTHFR gene polymorphism on total plasma homocysteine and folate levels in renal graft recipients, and its impact on chronic graft dysfunction and the associated endothelial dysfunction. Thirty two stable renal allograft recipients were included in this study [group I] and compared with age and sex matched thirty control subjects [group II]. Plasma homocysteine level, plasma folic acid level, plasma van Willebrand factor [vWF] activity together with endothelial dependent and independent brachial artery vascular responses were done for all subjects. MTHFR genotype was determined by PCR in all renal recipients who were further classified accordingly into 3 subgroups: [group Ia] with homozygous TT type, [group Ib] with heterozygous CT type, and [group Ic] is wild CC type. Renal allograft recipients showed significant higher level of homocysteine as compared to control group [44.42 +/- 32.08 vs 11.62 +/- 2.57 respectively, p<0.001]. There was significant endothelial dysfunction in the transplant group as evidenced by the higher vWF [119.71 +/- 17.71 vs 67.60 +/- 28.65 p<0.001] and poorer endothelial dependent dilatation [EDD] of the brachial artery [7.84 +/- 1.08 vs 12.68 +/- 0.96 p<0.001] as compared to the control group. There was significant negative correlation between plasma homocysteine level and creatinine clearance [r=-0.55, p=0.001], suggesting the deleterious effect of hyperhomocysteinaemia on graft function. The homozygous subgroup [gpIa] showed significant higher level of homocysteine, vWF, lower folic acid, creatinine clearance and EDD as compared to the other two subgroups [gp Ib and Ic]. Our study identified that the presence of hyperhomocysteinemia in combination with unfavorable MTHFR genotypes contributes to an increased risk for development of chronic allograft dysfunction