Risk of venous thromboembolism associated with single and combined effects of Factor V Leiden, Prothrombin 20210A and Methylenetethraydrofolate reductase C677T: a meta-analysis involving over 11,000 cases and 21,000 controls.

Genetic and environmental factors interact in determining the risk of venous thromboembolism (VTE). The risk associated with the polymorphic variants G1691A of factor V (Factor V Leiden, FVL), G20210A of prothrombin (PT20210A) and C677T of methylentetrahydrofolate reductase (C677T MTHFR) genes has been investigated in many studies. We performed a pooled analysis of case-control and cohort studies investigating in adults the association between each variant and VTE, published on Pubmed, Embase or Google through January 2010. Authors of eligible papers, were invited to provide all available individual data for the pooling. The Odds Ratio (OR) for first VTE associated with each variant, individually and combined with the others, were calculated with a random effect model, in heterozygotes and homozygotes (dominant model for FVL and PT20210A; recessive for C677T MTHFR). We analysed 31 databases, including 11,239 cases and 21,521 controls. No significant association with VTE was found for homozygous C677T MTHFR (OR: 1.38; 95 % confidence intervals [CI]: 0.98-1.93), whereas the risk was increased in carriers of either heterozygous FVL or PT20210 (OR = 4.22; 95 % CI: 3.35-5.32; and OR = 2.79;95 % CI: 2.25-3.46, respectively), in double heterozygotes (OR = 3.42; 95 %CI 1.64-7.13), and in homozygous FVL or PT20210A (OR = 11.45; 95 %CI: 6.79-19.29; and OR: 6.74 (CI 95 % 2.19-20.72), respectively). The stratified analyses showed a stronger effect of FVL on individuals ≤ 45 years (p value for interaction = 0.036) and of PT20210A in women using oral contraceptives (p-value for interaction = 0.045). In this large pooled analysis, inclusive of large studies like MEGA, no effect was found for C677T MTHFR on VTE; FVL and PT20210A were confirmed to be moderate risk factors. Notably, double carriers of the two genetic variants produced an impact on VTE risk significantly increased but weaker than previously thought.

Asociación entre hiperhomocisteinemia y esteatosis hepática en pacientes con hepatitis crónica C / Association of hyperhomocysteinemia with liver steatosis in patients with chronic hepatitis C

Fundamento y objetivo: La esteatosis hepática en la hepatitis crónica C (HCC) se relaciona con factores virales, metabólicos y posiblemente genéticos. El objetivo de este estudio es conocer si la hiperhomocisteinemia y el polimorfismo de la metilentetrahidrofolato reductasa (MTHFR)-C677T se asocian a esteatosis hepática en pacientes no alcohólicos con HCC. Pacientes y método: Se estudiaron 54 pacientes consecutivos diagnosticados de HCC mediante biopsia, con consumo de alcohol menor de 40g/semana, y sin otras causas de enfermedad hepática. Todas las variables se obtuvieron al tiempo de la biopsia. En 128 sujetos sanos, con edad y sexo similares a los pacientes, también se determinó el polimorfismo de la MTHFR-C677T. Resultados: Se encontró esteatosis hepática en 33 pacientes (61%), siendo en 30 de grado leve. En los pacientes con esteatosis existía una prevalencia más elevada de hiperhomocisteinemia (61% frente al 24%, p=0,008) y el sobrepeso tendía a ser más prevalente (61% frente al 33%, p=0,05). Todos los pacientes con genotipo 3 del virus C tenían esteatosis. La carga viral, actividad inflamatoria y fibrosis hepática no fueron diferentes en los pacientes con y sin esteatosis. El polimorfismo de la MTHFR-C677T fue similar en controles y casos, y en los casos con y sin esteatosis. La regresión logística múltiple mostró que la hiperhomocisteinemia se asociaba a esteatosis hepática tras ajustar por edad y sexo (odds ratio [OR] 3,94, intervalo de confianza del 95% [IC 95%] 1,09-14,29) y por sobrepeso (OR 4,43, IC 95% 1,27-15,51). Conclusiones: En pacientes no alcohólicos con HCC, la esteatosis hepática de grado leve es frecuente y se asocia a hiperhomocisteinemia. No se comprueba asociación de la esteatosis con el polimorfismo de la MTHFR-C677T (AU)

Background and objectives: Liver steatosis in chronic hepatitis C (CHC) is related to viral and metabolic factors and likely to genetic factors. The aim of this study was to know if hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR)-C677T polymorphisms are associated with liver steatosis in nonalcoholic patients with CHC.Patients and method: In 54 consecutive patients with CHC, alcohol consumption less than 40g/week, and no other causes of liver disease, a liver biopsy was performed. All variables were obtained at the time of biopsy. MTHFR-C677T was also performed in 128 healthy subjects, with age and gender similar to the patients. Results: Liver steatosis was found in 33 patients (61%), 30 of them having a mild degree. Hyperhomocysteinemia was more prevalent in patients with steatosis (61% vs 24%; p=0.008) and overweight tended to be more prevalent in the same patients (61% vs 33%; p=0.05). All patients with virus C genotype 3 had steatosis. Viral load, liver inflammatory and fibrosis score were not different in patients with and without steatosis. MTHFR-C677T polymorphism was similar in controls and cases and in cases with and without steatosis. A multiple logistic regression showed that hyperhomocysteinemia was associated with liver steatosis after adjustment for age and sex (OR: 3.94; 95% CI: 1.09-14.29), and adjustment for overweight (OR: 4.43; 95% CI: 1.27-15.51). Conclusions: In nonalcoholic patients with CHC mild liver steatosis is frequent, and is associated with hyperhomocysteinemia. An association between steatosis and MTHFR-C677T polymorphism was not found (AU)

[Association of hyperhomocysteinemia with liver steatosis in patients with chronic hepatitis C]. / Asociación entre hiperhomocisteinemia y esteatosis hepática en pacientes con hepatitis crónica C.

BACKGROUND AND OBJECTIVES: Liver steatosis in chronic hepatitis C (CHC) is related to viral and metabolic factors and likely to genetic factors. The aim of this study was to know if hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR)-C677T polymorphisms are associated with liver steatosis in nonalcoholic patients with CHC. PATIENTS AND METHOD: In 54 consecutive patients with CHC, alcohol consumption less than 40g/week, and no other causes of liver disease, a liver biopsy was performed. All variables were obtained at the time of biopsy. MTHFR-C677T was also performed in 128 healthy subjects, with age and gender similar to the patients. RESULTS: Liver steatosis was found in 33 patients (61%), 30 of them having a mild degree. Hyperhomocysteinemia was more prevalent in patients with steatosis (61% vs 24%; p=0.008) and overweight tended to be more prevalent in the same patients (61% vs 33%; p=0.05). All patients with virus C genotype 3 had steatosis. Viral load, liver inflammatory and fibrosis score were not different in patients with and without steatosis. MTHFR-C677T polymorphism was similar in controls and cases and in cases with and without steatosis. A multiple logistic regression showed that hyperhomocysteinemia was associated with liver steatosis after adjustment for age and sex (OR: 3.94; 95% CI: 1.09-14.29), and adjustment for overweight (OR: 4.43; 95% CI: 1.27-15.51). CONCLUSIONS: In nonalcoholic patients with CHC mild liver steatosis is frequent, and is associated with hyperhomocysteinemia. An association between steatosis and MTHFR-C677T polymorphism was not found.

La fibra dietética en la prevención del riesgo cardiovascular / Dietary fiber in the prevention of cardiovascular risk

La fibra dietética (FD) tiene numerosos beneficios para la salud entre los que hay que destacar el efecto protector cardiovascular, especialmente de la fibra soluble, avalado por grandes estudios clínicos y epidemiológicos. En ellos se evidencia el efecto beneficioso de la FD sobre la hipercolesterolemia, diabetes tipo 2,obesidad, hipertensión arterial, síndrome metabólico y proteína C reactiva como marcador de inflamación. Son también muchos los estudios epidemiológicos con FD en los que se comprueba tanto en varones como en mujeres una reducción del riesgo de enfermedad coronaria y cerebrovascular y posiblemente también de enfermedad arterial periférica. De acuerdo con estos hallazgos es aconsejable realizar una dieta rica en FD, sustituyendo los cereales refinados por los de grano entero y aumentando el consumo de vegetales y frutas, como una medida preventiva primaria contra la enfermedad cardiovascular (AU)

Dietary fiber (DF) has many health benefits. One of the most important is the cardiovascular protective effect, especially soluble fiber, supported by large clinical and epidemiologic studies. These verify the beneficial effect of DF on hypercholesterolemia, type 2 diabetes, obesity, hypertension, metabolic syndrome, and C-reactive protein as an inflammatory marker. There are also many epidemiologic studies in which DF has been shown to reduce the risk of coronary and cerebrovascular disease in both men and women, and possibly also peripheral arterial disease. According to these findings, it is advisable to make a diet rich in DF, replacing refined grains for whole grain and increasing consumption of fruits and vegetables, as a primary preventive measure against cardiovascular disease (AU)

[Increased homocysteine levels in polycystic ovary syndrome]. / Concentraciones elevadas de homocisteína en el síndrome de ovario poliquístico.

BACKGROUND AND OBJECTIVE: Women with polycystic ovary syndrome (PCOS) exhibit frequently risk factors that predispose to cardiovascular disease. Hyperhomocysteinemia is an independent risk factor for this disease. The aim of this study was to know whether young women with PCOS have increased homocysteine levels. We also analyzed their possible relation with folate and vitamin B12 levels. PATIENTS AND METHOD: Thirty nine patients with PCOS were studied; (age: mean [standard deviation] 28.9 [5.8] years), and 39 healthy women similar in age. We evaluated in all of them: smoking, menstrual cycles, hirsutism, body mass index, metabolic syndrome and levels of homocysteine, lipids, glucose, creatinine, folate, vitamin B12, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and androstendione. RESULTS: Menstrual cycles, hirsutism, androstendione, LH levels and LH/FSH were higher, as we expected, in patients with PCOS. Moreover, patients had increased homocysteine (9.1 [2.1] vs 6.4 [1.8] micromol/L; p < 0.001) and glucose levels (99 [13] vs 88 [10] mg/dl; p < 0.001), a higher frequency of abnormal fasting glycemia (> 110 mg/dl) (23% vs 2.5%; p =.01) and lower folate levels (7.6 [3.7] vs 10.2 [3.6] ng/ml; p = 0.02). A multiple linear regression showed a negative association between homocysteine and folate levels (r2 = 0.05; p =.02). CONCLUSIONS: Homocysteinemia is increased in women with PCOS, and it is negatively associated with folate levels.

Concentraciones elevadas de homocisteína en el síndrome de ovario poliquístico / Increased homocysteine levels in polycystic ovary syndrome

Fundamento y objetivo: En las mujeres con síndrome de ovario poliquístico (SOP) es frecuente que haya factores de riesgo que predispongan a tener enfermedad cardiovascular. Se sabe que la hiperhomocisteinemia es un factor de riesgo independiente para esta enfermedad. El objetivo del presente estudio ha sido conocer si las mujeres jóvenes con SOP presentan concentraciones elevadas de homocisteína, y su posible relación con las de folato y vitamina B12. Pacientes y método: Se seleccionó a 39 mujeres con SOP, con una edad media (desviación estándar [DE]) de 28,9 (5,8) años, y 39 mujeres sanas de edad similar, y en todas ellas se evaluaron: tabaquismo, ciclos menstruales, grado de hirsutismo, índice de masa corporal, presencia de síndrome metabólico y concentraciones de homocisteína, lípidos, glucosa, creatinina, folato, vitamina B12, folitropina (FSH), lutropina (LH) y androstendiona. Resultados: Los ciclos menstruales, el grado de hirsutismo, los valores de androstendiona y LH y la relación LH/FSH eran más elevados, como se esperaba, en las pacientes con SOP. Además, las pacientes presentaban valores más elevados de homocisteína (media [DE] de 9,1 [2,1] frente a 6,4 [1,8] mmol/l; p 110 mg/dl) (el 23 frente al 2,5%; p = 0,01) y unos valores más bajos de folato (media [DE] de 7,6 [3,7] frente a 10,2 [3,6] ng/ml; p = 0,02). En una regresión lineal múltiple, se comprobó una asociación negativa entre las concentraciones de homocisteína y las de folato (r2 = 0,05; p = 0,02). Conclusiones: La homocisteinemia es más elevada en las mujeres con SOP y se asocia negativamente a las concentraciones de folato

Background and objective: Women with polycystic ovary syndrome (PCOS) exhibit frequently risk factors that predispose to cardiovascular disease. Hyperhomocysteinemia is an independent risk factor for this disease. The aim of this study was to know whether young women with PCOS have increased homocysteine levels. We also analyzed their possible relation with folate and vitamin B12 levels. Patients and method: Thirty nine patients with PCOS were studied; (age: mean [standard deviation] 28.9 [5.8] years), and 39 healthy women similar in age. We evaluated in all of them: smoking, menstrual cycles, hirsutism, body mass index, metabolic syndrome and levels of homocysteine, lipids, glucose, creatinine, folate, vitamin B12, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and androstendione. Results: Menstrual cycles, hirsutism, androstendione, LH levels and LH/FSH were higher, as we expected, in patients with PCOS. Moreover, patients had increased homocysteine (9.1 [2.1] vs 6.4 [1.8] mmol/L; p 110 mg/dl) (23% vs 2.5%; p =.01) and lower folate levels (7.6 [3.7] vs 10.2 [3.6] ng/ml; p = 0.02). A multiple linear regression showed a negative association between homocysteine and folate levels (r2 = 0.05; p =.02). Conclusions: Homocysteinemia is increased in women with PCOS, and it is negatively associated with folate levels

[New perspectives in the measurement of cardiovascular risk: explorations to detect subclinical atherosclerosis and inflammation markers]. / Nuevas perspectivas en la medición del riesgo cardiovascular: exploraciones para detectar la aterosclerosis subclínica y marcadores de inflamación.

Among the new technologies for the detection of subclinical atherosclerosis, ankle-brachial index, carotid ultrasonography, computed tomography detection of coronary calcifications and high-resolution nuclear magnetic resonance are those of greatest clinical usefulness. These explorations are especially useful for patients with an intermediate cardiovascular risk, or a 10-20% risk according to the National Cholesterol Education Program-Adult Treatment Panel III or 3-4% according to the SCORE project. This is because they allow the identification of high-risk patients who need a more intense treatment. In addition, high-sensitivity C-reactive protein concentrations may be considered as a new marker for the evaluation of cardiovascular risk. In this article, the current state of knowledge about these explorations and the guidelines of the main scientific societies are reviewed, and the practical conclusions of the working group are provided.

Nuevas perspectivas en la medición del riesgo cardiovascular: exploraciones para detectar la aterosclerosis subclínica y marcadores de inflamación / New perspectives in the measurement of cardiovascular risk: explorations to detect sublicinical atherosclerosis and inflammation markers

Entre las nuevas técnicas para la detección de la aterosclerosis subclínica, las de mayor utilidad son la medición del índice tobillo-brazo, la ecografía carotídea, la tomografía computarizada para la detección de calcio coronario y la resonancia magnética de alta resolución. Estas técnicas son especialmente útiles para la evaluación de los pacientes de riesgo cardiovascular intermedio, es decir un 10-20% según el National Cholesterol Education Program-Adult Treatment Panel III o un 3-4% según el proyecto SCORE, ya que permiten identificar a los que presentan un alto riesgo y precisarán un tratamiento más enérgico. Asimismo, se puede considerar la proteína C reactiva de alta sensibilidad como un nuevo marcador para la evaluación del riesgo cardiovascular. En este trabajo se revisa el estado actual de los conocimientos sobre esas exploraciones y las recomendaciones de las principales sociedades científicas y se incluyen las conclusiones prácticas del grupo de trabajo sobre su utilización clínica

Among the new technologies for the detection of subclinical atherosclerosis, ankle-brachial index, carotid ultrasonography, computed tomography detection of coronary calcifications and high-resolution nuclear magnetic resonance are those of greatest clinical usefulness. These explorations are especially useful for patients with an intermediate cardiovascular risk, or a 10-20% risk according to the National Cholesterol Education Program-Adult Treatment Panel III or 3-4% according to the SCORE project. This is because they allow the identification of high-risk patients who need a more intense treatment. In addition, high-sensitivity C-reactive protein concentrations may be considered as a new marker for the evaluation of cardiovascular risk. In this article, the current state of knowledge about these explorations and the guidelines of the main scientific societies are reviewed, and the practical conclusions of the working group are provided

Effect of folic acid treatment on carotid intima-media thickness of patients with coronary disease.

BACKGROUND: Carotid intima-media thickness (CIMT) is a surrogate marker of cardiovascular morbility. Hyperhomocysteinemia, which is an independent cardiovascular risk factor, is associated with low folate levels. The aim of this study was to evaluate the effect of folic acid treatment on the evolution of CIMT in patients with coronary disease and homocysteinemia > or =9 micromol/l. METHODS: In 137 consecutive patients with coronary disease treated with statins and normal vitamin B12 values, a randomized treatment with open-label folic acid 2.5 mg/day (group A) or not (group B) was performed during 3 years. CIMT was evaluated by two-dimensional ultrasonography baseline and at the final of the study. RESULTS: Clinical, biochemical parameters and CIMT were similar in both groups of patients. Homocysteine levels decreased (12.4+/-3.4 vs. 10.3+/-2.4 micromol/l; p<0.001) in group A, but not in group B. CIMT did not change neither in group A (0.71+/-0.23 vs. 0.69+/-0.20 mm; p=0.34) nor in group B (0.74+/-0.23 vs. 0.72+/-0.29 mm; p=0.39). In 12 patients of group A with methylenetetrahydrofolate reductase (MTHFR) 677TT mutation a decrease of CIMT was found (0.83+/-0.35 vs. 0.72+/-0.27 mm; p=0.02), but a multiple linear regression only showed a trend to the association between CIMT changes and MTHFR 677TT (p=0.051), probably due to the small number of patients with this mutation. CONCLUSIONS: Long-time treatment with folic acid in patients with coronary disease and normal values of vitamin B12 decreases homocysteine levels. A CIMT decrease is observed in treated patients with MTHFR 677TT mutation.

[Hyperhomocysteinemia and treatment with antiepileptic drugs. Effects of different doses of folic acid]. / Hiperhomocisteinemia en pacientes tratados con antiepilépticos. Efecto de diferentes dosis de ácido fólico.

BACKGROUND AND OBJECTIVE: An increase homocysteine values, which is an independent risk factor for atherotrombotic disease, can be produced with antiepileptic treatment. The aims of this study were: 1) to assess the frequency and determinant factors of hyperhomocysteinemia in adult patients receiving antiepileptic drugs, and 2) to know the effect of different doses of folic acid. PATIENTS AND METHOD: Ninety eight patients and 100 healthy controls similar in age and gender were studied. Eighty six patients were treated with hepatic enzyme inductors (diphenylhydantoine and/or phenobarbital and/or primidone and/or carbamazepine), 5 received non inductors (valproate) and 7 were treated with both in combination. Thirty eight patients were randomized to receive in an open and concurrent way folic acid, 0.2 mg (n = 18) or 5.2 mg (n = 20) daily for 3 months. RESULTS: Homocysteine values were increased in patients in relation with controls (mean [SD]12.2 [6.7] 95% confidence interval [CI],10.0-13.5 vs 8.8[2.2] 95% CI, 8.3-9.2 micromol/l; p < 0.001). Hyperhomocysteinemia was found in 28 patients and 4 controls (28.6% vs 4.0%; p < 0.001). In a multivariate analysis hyperhomocysteinemia was positively associated with treatment with antiepileptic inductors and negatively with folate values and female gender. Homocysteine values decreased after treatment with folic acid at high and low doses (p < 0.001 for both groups), and the values observed in the latter group were similar to those in healthy controls. CONCLUSIONS: Hyperhomocysteinemia is frequent in patients treated with antiepileptic drugs. Treatment with hepatic enzyme inductors and low folate values are predictors of hyperhomocysteinemia. Administration of folic acid, even at very low doses, produces a significant decrease of homocysteinemia in these patients.

[Effect of hyperhomocysteinemia and methylenetetrahydrofolate reductase 677C --> T mutation in venous thromboembolism risk of young adults]. / Efecto de la hiperhomocisteinemia y de la mutación metilentetrahidrofolato reductasa 677C --> T en el riesgo de tromboembolia venosa en adultos jóvenes.

BACKGROUND AND OBJECTIVE: To investigate whether hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) 677C --> T mutation are associated with venous thromboembolism in young Spanish adults. PATIENTS AND METHOD: One hundred adult patients younger than 50 years and 177 controls with similar age and gender. RESULTS: Hyperhomocysteinemia was present in 21% of the patients and 3.3% of the controls (p < 0.001), and MTHFR 677C --> T mutation was found in 25 and 14.7%, respectively (p = 0.03). Odds ratio (OR) for thromboembolism in hyperhomocysteinemic patients was 7.5 (95% CI, 2.9-19.2; p < 0.001), and in patients with MTHFR 677C --> T mutation the OR was 1.9 (95% CI, 1.1-3.5; p = 0.03). In a subgroup of 76 patients without other thrombogenic factors, thromboembolism persisted associated with hyperhomocysteinemia, yet an association with MTHFR 677C --> T mutation was not confirmed. CONCLUSIONS: Hyperhomocysteinemia, but not MTHFR 677C --> T mutation, is a risk factor for venous thromboembolism in young adults without other thrombogenic factors.

Hiperhomocisteinemia en pacientes tratados con antiepilépticos. Efecto de diferentes dosis de ácido fólico / Hyperhomocysteinemia and treatment with antiepileptic drugs. Effects of different doses of folic acid

FUNDAMENTO Y OBJETIVO: La elevación de la homocisteína, que es un factor de riesgo de enfermedad aterotrombótica, puede producirse con la administración de antiepilépticos. Los objetivos de este estudio han sido: a) evaluar la frecuencia y los factores determinantes de hiperhomocisteinemia en pacientes adultos tratados con antiepilépticos, y b) conocer el efecto de diferentes dosis de ácido fólico sobre los valores de homocisteína plasmática. PACIENTES Y MÉTODO: Se estudió a 98 pacientes y a 100 controles sanos con edad y sexo similares. De los pacientes, 86 recibían tratamiento con inductores de enzimas hepáticas (difenilhidantoínay/o fenobarbital y/o primidona y/o carbamacepina), 5 con no inductores (valproato) y 7 con combinación de ambos. Treinta y ocho pacientes se trataron aleatoriamente de forma abierta y concurrente con 0,2 mg (n = 18) o 5,2 mg (n = 20) de ácido fólico diariamente durante 3 meses. RESULTADOS: Las concentraciones de homocisteína estaban aumentadas en los pacientes en relación con los controles (media [desviación estándar] 12,2 [6,7] µmol/l intervalo de confianza del 95%,10,0-13,5, frente a 8,8 [2,2] µmol/l; intervalo de confianza del 95%, 8,3-9,2 µmol/l;p < 0,001). En 28 pacientes y en 4 controles existía hiperhomocisteinemia (el 28,6 frente al4,0%; p < 0,001). En el análisis multivariante, la hiperhomocisteinemia se asoció positivamente al tratamiento con antiepilépticos inductores y negativamente a los valores de folato y al sexo femenino. La homocisteinemia descendió significativamente tras el tratamiento con ácido fólico, tanto en dosis altas como bajas (p < 0,001 para ambos grupos), y en este último grupo se obtuvieron concentraciones similares a las de los controles sanos. CONCLUSIONES: La hiperhomocisteinemia es frecuente en los pacientes tratados con antiepilépticos. El tratamiento con inductores de las enzimas hepáticas y los valores bajos de folato son predictores de hiperhomocisteinemia. El tratamiento con ácido fólico, incluso a dosis muy bajas, disminuye significativamente la homocisteinemia en estos pacientes

BACKGROUND AND OBJECTIVE: An increase homocysteine values, wich is an independent risk factor for atherotrombotic disease, can be produced with antiepileptic treatment. The aims of this study were: 1) to assess the frequency and determinant factors of hyperhomocysteinemia in adult patients receiving antiepileptic drugs, and 2) to know the effect of different doses of folic acid. PATIENTS AND METHOD: Ninety eight patients and 100 healthy controls similar in age and gender were studied. Eigthy six patients were treated with hepatic enzyme inductors (diphenylhydantoine and/or phenobarbital and/or prim done and/or carbamazepine), 5 received non inductors (valproate)and 7 were treated with both in combination. Thirty eight patients were randomized to receive in an open and concurrent way folic acid, 0.2 mg (n = 18) or 5.2 mg (n = 20) daily for 3 months. RESULTS: Homocysteine values were increased in patients in relation with controls (mean[SD]12.2 [6.7] 95% confidence interval [CI],10,0-13,5 vs 8.8[2.2] 95% CI, 8,3-9,2 µmol/l;p < 0.001). Hyperhomocysteinemia was found in 28 patients and 4 controls (28.6% vs 4.0%;p < 0.001). In a multivariate analysis hyperhomocysteinemia was positively associated with treatment with antiepileptic inductors and negatively with folate values and female gender. Homocysteine values decreased after treatment with folic acid at high and low doses (p < 0.001 for both groups), and the values observed in the latter group were similar to those in healthy controls. CONCLUSIONS: Hyperhomocysteinemia is frequent in patients treated with antiepileptic drugs. Treatment with hepatic enzyme inductors and low folate values are predictors of hyperhomocysteinemia. Administration of folic acid, even at very low doses, produces a significant decrease of homocysteinemia in these patients

Efecto de la hiperhomocisteinemia y de la mutación metilentetrahidrofolato reductasa 677C → T en el riesgo de tromboembolia venosa en adultos jóvenes / Effect of hyperhomocysteinemia and methylenetetrahydrofolate reductase 677C-> T mutation in venous thromboembolism risk of young adults

FUNDAMENTO Y OBJETIVO: Conocer si la hiperhomocisteinemia y la mutación de la metilentetra hidrofolatoreductasa (MTHFR) 677C→T se asocian a la tromboembolia venosa en adultos jóvenes españoles. PACIENTES Y MÉTODO: Se estudiaron 100 pacientes adultos menores de 50 años y 177 controles con edad y sexo similar a la de los pacientes. RESULTADOS: Se comprobó la hiperhomocisteinemia en el 21% de los pacientes y en el3,3% de los controles (p < 0,001) y la mutación MTHFR 677C→T en el 25 y en el 14,7%de ambos grupos, respectivamente (p = 0,03).La odds ratio (OR) de tromboembolia en los pacientes con hiperhomocisteinemia fue de7,5 (intervalo de confianza [IC] del 95%, 2,9-19,2; p < 0,001) y en los pacientes con la mutación MTHFR 677C→T fue de 1,9; (IC del95%, 1,1-3,5; p = 0,03). En un subgrupo de76 pacientes sin otros factores trombogénicos, la enfermedad tromboembólica persistía asociada a la hiperhomocisteinemia, pero no a la mutación MTHFR 677C→T.CONCLUSIONES: La hiperhomocisteinemia, aunque no la mutación MTHFR 677C→T, es un factor de riesgo de tromboembolia venosa en adultos jóvenes sin otros factores trombogénicos

BACKGROUND AND OBJECTIVE: To investigate whether hyperhomocysteinemia and methylenetetrahydrofolatereductase (MTHFR) 677C→Tmutation are associated with venous thromboembolismin young Spanish adults. PATIENTS AND METHOD: One hundred adult patients younger than 50 years and 177 controls with similar age and gender. RESULTS: Hyperhomocysteinemia was present in 21% of the patients and 3.3% of the controls (p < 0.001), and MTHFR 677C→T mutation was found in 25 and 14.7%, respectively(p = 0.03). Odds ratio (OR) for thromboembolismin hyperhomocysteinemic patients was7.5 (95% CI, 2.9-19.2; p < 0.001), and inpatients with MTHFR 677C→T mutation the OR was 1.9 (95% CI, 1.1-3.5; p = 0.03). In a subgroup of 76 patients without other thrombogenic factors, thromboembolism persisted associated with hyperhomocysteinemia, yet an association with MTHFR 677C→T mutation was not confirmed. CONCLUSIONS: Hyperhomocysteinemia, but not MTHFR 677C→T mutation, is a risk factor for venous throm

Apolipoprotein E polymorphism and carotid atherosclerosis in patients with coronary disease.

BACKGROUND: Apolipoprotein (apo) E polymorphism plays a role in the development of coronary disease, but their involvement in carotid atherosclerosis is controversial. The aim of this study was to evaluate the role of apo E polymorphism in the development of subclinical carotid atherosclerosis in patients with coronary disease. METHODS: In 226 consecutive patients with coronary disease, apo E genotypes were performed by PCR and restriction analysis. Intima-media thickness (IMT) and the presence of atherosclerotic plaques in carotid arteries were evaluated by two-dimension ultrasonography. RESULTS: Apo E allele frequencies were: 3=0.70, 4=0.22 and 2=0.08. The only patient with 2/4 genotype was excluded for the analysis. The patients were divided in three groups according to apo E genotype: E2 (2/2, 2/3), E3 (3/3) and E4 (4/4, 4/3). Patients of E4 group had higher values of low-density-lipoprotein (LDL) cholesterol and apo B than patients of E2 group (P< or =0.01). Carotid IMT mean was not different in E3 (0.81+/-0.21 mm), E4 (0.83+/-0.23 mm) and E2 groups (0.76+/-0.17 mm) (P=0.52). Mean differences of IMT in E3 group were not different from those of E2 or E4 groups after adjusting for age and gender in a first analysis, and for age, gender and LDL cholesterol levels in a second one. The number of plaques in apo E3 group was similar to that in apo E2 or apo E4 groups, after adjusting for the same variables. CONCLUSIONS: A relationship between subclinical carotid atherosclerosis and apo E polymorphism is not found in patients with coronary disease.

[Homocysteine and progression of carotid atherosclerosis in patients with coronary disease]. / Homocisteína y progresión de la aterosclerosis de la arteria carótida en pacientes con enfermedad coronaria.

BACKGROUND AND OBJECTIVE: Carotid intima-media thickness (IMT) is a marker of generalized atherosclerosis. Sequential evaluation of carotid IMT has permitted to know the factors involved in its progression. However, there are few studies about the influence of homocysteine in such progression. The aim of this work was to know the effect of homocysteine values on the evolution of carotid IMT in patients with coronary disease. PATIENTS AND METHOD: Carotid IMT (baseline and after 4 years of follow-up) was evaluated by a B-mode ultrasonography in 187 patients with coronary disease (166 males and 21 females; age: mean [standard deviation], 60 [7] years); 185 patients were treated with statins from the beginning of the study. RESULTS: Carotid IMT progression was confirmed in 59 patients (31.6%; 95% confidence interval [CI], 25.0-38.7%). Cardiovascular risk factors, basal biochemical parameters and methylenetetrahydrofolate reductase-C677T polymorphism were similar in patients with and without progression except for homocysteine values which were higher in the former (13.3 [5.3]; 95% CI, 12.0-14.6 vs 11.1 [3.5]; 95% CI, 10.5-11.7 (mol/l; p = 0.001). Biochemical changes at the end of the study were similar in both groups. In the multivariate analysis, IMT progression was associated with basal values of homocysteine (odds ratio [OR] 1.19; 95% CI, 1.07-1.31; p = 0.0008), female gender (OR 3.50; 95% CI, 1.17-10.50; p = 0.02), hypertension (OR 2.52; 95% CI, 1.14-5.59; p = 0.02) and basal high-density lipoprotein (HDL)-cholesterol values (OR, 0.94; 95% CI, 0.90-0.98; p = 0.009). CONCLUSIONS: The concentration of homocysteine is associated with the progression of carotid atherosclerosis in patients with coronary heart disease treated with statins.

Homocisteína y progresión de la aterosclerosis de la arteria carótida en pacientes con enfermedad coronaria / Homocysteine and progression of carotid atherosclerosis in patients with coronary disease

FUNDAMENTO Y OBJETIVO: El grosor íntima-media (GIM) de la arteria carótida es un marcador de aterosclerosis generalizada. La evaluación secuencial del GIM ha permitido conocer los factores implicados en su progresión. Sin embargo, hay pocos estudios que valoren el efecto de la homocisteína en esta progresión. El objetivo de este trabajo ha sido conocer si los valores de homocisteína influyen en la evolución del GIM carotídeo en pacientes con enfermedad coronaria. PACIENTES Y MÉTODO: Se evaluó el GIM de la arteria carótida común basalmente y a los 4 años de seguimiento mediante una ecografía bidimensional en 187 pacientes con enfermedad coronaria (166 varones y 21 mujeres con una edad media [desviación estándar] de 60 [7] años); 185 pacientes se trataron con estatinas desde el comienzo del estudio. RESULTADOS: Se comprobó progresión del GIM carotídeo en 59 pacientes (31,6 por ciento; intervalo de confianza [IC] del 95 por ciento, 25,0-38,7 por ciento). Los factores de riesgo cardiovascular, los parámetros bioquímicos basales y el polimorfismo de la metilentetrahidrofolato reductasa-C677T eran similares en los pacientes con progresión y sin ella, a excepción de los valores de homocisteína que eran superiores en los primeros (13,3 [5,3] con un IC del 95 por ciento de 12,0-14,6 µmol/l frente a 11,1 [3,5] con un IC del 95 por ciento de 10,5-11,7 µmol/l; p = 0,001). Los cambios bioquímicos evidenciados al final del estudio no fueron diferentes en los dos grupos. El análisis multivariante demostró que la progresión del GIM se asociaba con los valores basales de homocisteína (odds ratio [OR] = 1,19; IC del 95 por ciento, 1,07-1,31; p = 0,0008) con el sexo femenino (OR = 3,50; IC del 95 por ciento, 1,17-10,50; p = 0,02), con la hipertensión (OR = 2,52; IC del 95 por ciento, 1,145,59; p = 0,02) y con los valores basales de colesterol unido a las lipoproteínas de alta densidad (OR = 0,94; IC del 95 por ciento, 0,90-0,98; p = 0,009). CONCLUSIONES: Las concentraciones de homocisteína se asocian a la progresión de la aterosclerosis carotídea en pacientes con enfermedad coronaria tratados con estatinas. (AU)

Aspirina y marcadores de inflamación en pacientes con enfermedad coronaria / Aspirin and inflammatory markers in patients with coronary disease

No disponible

Cardiovascular risk factors in 116 patients 5 years or more after liver transplantation.

We assessed the cardiovascular risk factors (CVRFs) in 116 stable liver transplant patients surviving for 5 years or more (median: 102 months). The prevalence of smokers was 29.3%, hypertension 49.1%, obesity 22.4%, hypercholesterolemia 34.5%, hypertriglyceridemia 11.2%, and hyperhomocysteinemia 57.8%. Diabetes was found in 21.5% of the patients, being more frequent in patients with hepatitis-C-virus infection (31.8% vs 15.3%; P=0.03). Patients on cyclosporine therapy had a higher prevalence of hypertension, hypercholesterolemia and hyperhomocysteinemia than those treated with tacrolimus. Multivariate analysis showed only an association between cyclosporine therapy and cholesterol concentrations (odds ratio:1.02; 95% confidence interval (CI): 1.00-1.03; P=0.01). The prevalence of hypertension, diabetes, hypercholesterolemia and hypertriglyceridemia was lower at the time of the study than at 1 and 3 years after transplantation ( P<0.05), probably related to steroid withdrawal. Comparing 87 patients' CVRFs with the general Spanish population, we found that the age-gender standardized prevalence ratio was not different: smoking 1.46 (95% CI: 0.88-1.76), obesity 1.16 (95% CI: 0.60-1.44), hypertension 1.55 (95% CI: 0.98-1.81), and hypercholesterolemia 0.64 (95%CI: 0.35-1.90). We conclude that the prevalence of CVRFs in liver transplant patients after 5 years or more is lower that found in the first years after the transplantation, and no different from that found within the Spanish population.