La ecografía carotídea es útil para predecir enfermedad coronaria y mortalidad en pacientes en hemodiálisis / Prognostic value of carotid intima media thickness and wall plaques in hemodialysis patients

Introducción: La enfermedad cardiovascular es la principal causa de muerte en los pacientes urémicos en hemodiálisis (HD). La ecografía carotídea es una herramienta sencilla y no invasiva para conocer el estado aterosclerótico de los pacientes. Objetivo: Conocer las asociaciones clínicas del grosor íntima-media carotídeo (GIM) y de la placa carotí- dea y su valor predictivo sobre el riesgo de enfermedad co- ronaria y la mortalidad. Metodología: Estudio prospectivo en el que se incluyeron 60 pacientes estables en HD (68 ± 13 años, 48% hombres, 50% diabéticos, tiempo en HD de 32 ± 11 meses) y 274 controles, semejantes en edad y sexo. El período de seguimiento fue de 66 ± 13 meses. Determi- naciones: Datos demográficos y clínicos, analítica general y niveles séricos de homocisteína y folato. Se midió el GIM mediante ecocardiografía 2D. Resultados: El GIM fue mayor en los pacientes en HD que en el grupo control (0,947 ± 0,308 frente a 0,619 ± 0,176 mm; p <0,001). El GIM se correlacionó con la edad (r = 0,268; p = 0,038), con la condición de diabético (r = 0,650; p <0,001) y la de hiper- tenso (r = 0,333; p = 0,012), pero no con colesterol total, HDL, LDL, triglicéridos, homocisteína o folato. Los pacien- tes con enfermedad coronaria, enfermedad vascular peri- férica o ictus tenían un GIM mayor que los que no presen- taban dichas afecciones (1,156 ± 0,371 frente a 0,875 ± 0,285 mm; p <0,001; 1,205 ± 0,374 frente a 0,911 ± 0,231 mm; p = 0,007; 1,195 ± 0,264 frente a 0,844 ± 0,251; p <0,001, respectivamente). Se encontraron datos similares respecto a la presencia de placas en la pared carotídea. Durante el período de seguimiento fallecieron 36 pacientes, 24 de los cuales (67%) por causa cardiovascular, cuyo GIM fue mayor (1,020 ± 0,264 frente a 0,858 ± 0,334 mm; p = 0,044). La supervivencia a la finalización del período de es- tudio fue significativamente mejor en el cuartil inferior de GIM (72%) que en el superior (20%). La presencia de pla- cas carotídeas fue predictor independiente de mortalidad cardiovascular. Conclusiones: El GIM y las presencia de pla- cas carotídeas se relacionan con algunos de los factores clá- sicos de riesgo cardiovascular como la edad, la diabetes o la hipertensión en pacientes urémicos. Su medición es útil para predecir la enfermedad coronaria y la mortalidad a largo plazo en los paciente urémicos (AU)

ntroduction: Cardiovascular disease and other complica- tions of atherosclerosis are the most common cause of death in patients with chronic renal failure in maintenance hemodialysis (MHD). Carotid ultrasonography is a simple no invasive tool to investigate the vascular system, by means of intima media thickness (IMT) measurement and carotid wall calcifications. Objective: To determine IMT and the presence of plaques, and their possible clinical re- lationships; finally we tried to investigate whether they would predict cardiovascular morbidity and mortality in patients in MHD. Methods: We studied 60 MHD patients (age 68 ± 13 years, 48% male, 50% diabetics, tiem on MHD 32 ± 11 months) and a control group of 274 people matched for age and sex. Follow-up period was 66 ± 13 months. Measurements: Demographic and clinical data, serum levels of homocysteine (tHcy), folic acid (FA) and B 6 and B 12 vitamins. IMT was measured by high-resolution B- mode ultrasonography. Results: IMT was higher in MHD patients than in those in the control group (0.947 ± 0.308 vs 0.619 ± 0.176 mm; P <0.001). IMT was related with age (r = 0.268; P = 0.038), diabetic (r = 0.650; P <0.001) and hy- pertensive condition (r = 0.333; P = 0.012), but not wih lipids, tHcy or FA. Similar findings were found with the presence or not of carotid plaques but serum LDL-choles- terol levels were also related (r= –0.280; P = 0.031). Patients who suffered from coronary artery disease, peripheral ar- tery disease or stroke had higher IMT than those without those events (1.156 ± 0.371 vs 0.875 ± 0.285 mm; P <0.001; 1.205 ± 0.374 vs 0.911 ± 0.231 mm; P = 0.007; 1.195 ± 0.264 vs 0.844 ± 0.251; P <0.001 respectively). Something similar ocurred with the presence of plaques. During the follow- up period 36 patients (60%) died, 67% of them due to car- diovascular causes. IMT was higher in patients who expired than those who survived (1.020 ± 0.264 vs 0.858 ± 0.334 mm; P = 0.044). The survival rate during the observation was significantly lower in the final IMT fourth (20%) than in the first (72%) (P = 0.014). The presence of carotid plaques was an independent predictor of cardiovascular mortality. Conclusions: These findings suggests that meas- urement of carotid IMT and the presence of wall plaques are useful tools to predict cardiovascular events and mor- tality in patients in MHD (AU)

[Carotid ultrasound: prevention of heart disease and mortality on haemodialysis]. / La ecografía carotídea es útil para predecir enfermedad coronaria y mortalidad en pacientes en hemodiálisis.

INTRODUCTION: Cardiovascular disease and other complications of atherosclerosis are the most common cause of death in patients with chronic renal failure in maintenance hemodialysis (MHD). Carotid ultrasonography is a simple non-invasive tool to investigate the vascular system, by means of intima media thickness (IMT) measurement and carotid wall calcifications. OBJECTIVE: To determine IMT and the presence of plaques, and their possible clinical relationships; finally we tried to investigate whether they would predict cardiovascular morbidity and mortality in patients in MHD. METHODS: We studied 60 MHD patients (age 68 +/- 13 years, 48% male, 50% diabetics, time on MHD 32 +/- 11 months) and a control group of 274 people matched for age and sex. Follow-up period was 66 +/- 13 months. MEASUREMENTS: Demographic and clinical data, serum levels of homocysteine (tHcy), folic acid (FA) and B6 and B12 vitamins. IMT was measured by high-resolution B-mode ultrasonography. RESULTS: IMT was higher in MHD patients than in those in the control group (0.947 +/- 0.308 vs 0.619 +/- 0.176 mm; P < 0.001). IMT was related with age (r = 0.268; P = 0.038), diabetic (r = 0.650; P < 0.001) and hypertensive condition (r = 0.333; P = 0.012), but not wih lipids, tHcy or FA. Patients who suffered from coronary artery disease, peripheral artery disease or stroke had higher IMT than those without those events (1.156 +/- 0.371 vs 0.875 +/- 0.285 mm; P < 0.001; 1.205 +/- 0.374 vs 0.911 +/- 0.231 mm; P = 0.007; 1.195 +/- 0.264 vs 0.844 +/- 0.251; P < 0.001 respectively). Something similar occurred with the presence of plaques. During the follow-up period 36 patients died (60%), 67% of them due to cardiovascular causes. IMT was higher in patients who died than those who survived (1.020 +/- 0.264 vs 0.858 +/- 0.334 mm; P = 0.044). The survival rate during the observation period was significantly lower in the final IMT fourth (20%) than in the first (72%) (P = 0.014). The presence of carotid plaques was an independent predictor of cardiovascular mortality. CONCLUSIONS: These findings suggests that measurement of carotid IMT and the presence of wall plaques are useful tools to predict cardiovascular events and mortality in patients in MHD.

[Efficacy and safety of two vitamin supplement regimens on homocysteine levels in hemodialysis patients. Prospective, randomized clinical trial]. / Eficacia y seguridad de dos pautas de suplementos vitamínicos sobre los niveles de homocisteína en pacientes en hemodiálisis. Ensayo clínico prospectivo y randomizado.

UNLABELLED: High levels of homocysteine (tHcy) are frecuent in MHD patients, and recognized as a risk factor for cardiovascular events. Vitamin supplements have been shown to lower serum Hcys, although optimal dose and efficacy is not well defined. Moreover, methylenetetrahydrofolate reductase (MTHFR) gene polymorphism can modulate its prevalence and response to treatment. OBJECTIVE: To evaluate efficacy and safety of two vitamin supplement regimens on Hcys serum levels over a 12 month period. METHODS: We conducted a prospective, randomised, double-blind trial in 60 stable MHD patients (68 +/- 13 years, 48% male, 50% diabetics). Patients were randomly assigned to one of two treatment regimens: 1) daily renal multivitamin containing folate (FA), vitamin B6 and B12 (5 mg, 10 mg and 0.4 mg respectively) (N = 27); and 2) supraphysiological daily doses (15 mg, 100 mg and 1 mg) (N = 33). These regimens were continued throughout the study period. Hcys levels were compared with a control group from the general population (N = 276) matched for age and gender. MEASUREMENTS: demographic and clinical data, serum levels of Hcys, FA, B6, B12 at baseline and after 1, 3, 6 and 12 months of treatment; MTHFR gene polymorphism (PCRRT). RESULTS: At baseline, global prevalence of hyperhomocysteinemia (tHcy > or = 15 micromol/L) was 100% in patients and 22% en controls. Hcys levels were significantly higher in patients versus controls (32.4 +/- 8.9 vs 12.9 +/- 6.8; P < 0.0001). Both regimens were equally effective in reducing Hcys levels. As a whole, Hcys levels were reduced by 23.6% (P < 0.001) after one month of treatment. The highest reduction was observed at the sixth month (28.3%, 32.4 +/- 8.9 vs 22.7 +/- 6.4, P < 0.001) and remained stable thereafter. However, only 12% of patients normalised their plasma levels after 12 months of therapy. The effect of treatment was not influenced by age, gender, diabetes, body weight or time on MHD. Reduction rate of tHcy levels was related to baseline tHcy level (r = 0.500, P < 0.001) and baseline FA levels (r = -0.332, P = 0.009). The MTHFR polimorfism did not significantly modified the effect of the treatment. No side effects were associated with either regimen. CONCLUSIONS: Hyperhomocysteinemia is common in patients with conventional HD schedules and this is not related to vitamin deficiencies. Vitamin supplements significantly reduce Hcys levels in a sustained but suboptimal way. Supraphysiological doses did not improve the results. Further studies are requiered to demonstrate that this effect is associated with an improval in morbidity and mortality.

Eficacia y seguridad de dos pautas de suplementos vitamínicos sobre los niveles de homocisteína en pacientes en hemodiálisis. Ensayo clínico prospectivo y randomizado / Efficacy and safety of two vitamin supplement regimens on hyperhomocysteinemia in maintenance hemodialysis (MHD) patients

La hiperhomocisteinemia (HHcys) es frecuente en pacientes urémicos y representaun factor de riesgo cardiovascular. Los suplementos vitamínicos reducen losniveles de homocisteína (Hcys), no estando bien definida la dosis óptima y su eficacia.El genotipo de la metilentetrahidrofolatoreductasa (MTHFR) puede modularsu prevalencia y respuesta al tratamiento.Objetivo: Conocer la eficacia de dos pautas de suplementos vitamínicos sobrelos niveles de Hcys tras 12 meses de tratamiento.Metodología: Estudio prospectivo, randomizado, a doble ciego. Sesenta pacientesen hemodiálisis se aleatorizaron en dos grupos terapéuticos: A) Dosis habituales deácido fólico (AcF), vitamina B6 y B12 a la dosis de 5, 10 y 0,4 mg diarios, respectivamente(N = 27) y B) Dosis suprafisiológicas (15, 100 y 1 mg diarios) (N = 33).Los valores de Hcys se compararon con un grupo control similar en edad y sexo.Resultados: Todos los pacientes y el 22% de los controles presentaron HHcyssiendo los niveles de Hcys 2,5 veces superiores en los pacientes que en el grupocontrol (32,4 ± 8,9 vs 12,9 ± 6,8 µmol/L; P < 0,0001). Las dos pautas fueron igualmenteeficaces en reducir la Hcys, aunque solamente el 12% de los pacientes normalizaronsus niveles al finalizar el estudio. Globalmente, los niveles de Hcys experimentaronun descenso significativo al mes de tratamiento (23,6%, P < 0,001).El mayor descenso se registró tras 6 meses (28,3%, P < 0,001), estabilizándose hastalos 12 meses. El mayor descenso de Hcys se asoció con niveles basales más altosde Hcys (r = 0,500, P < 0,001) y más bajos de AcF (r = -0,332, P = 0,009). El polimorfismode la MTHFR no modificó significativamente la respuesta terapéutica.Conclusiones: La HHcys es constante con pautas convencionales de hemodiálisisaunque no existan déficits vitamínicos. Los suplementos reducen de forma substancialy sostenida los niveles de Hcys. Dosis suprafisiológicas no suponen ventajasadicionales. Se requieren nuevos estudios para demostrar que este descensoconlleve un impacto final favorable sobre la morbi-mortalidad cardiovascular

High levels of homocysteine (tHcy) are frecuent in MHD patients, and recognizedas a risk factor for cardiovascular events. Vitamin supplements have beenshown to lower serum Hcys, although optimal dose and efficacy is not well defined.Moreover, methylenetetrahydrofolate reductase (MTHFR) gene polymorphismcan modulate its prevalence and response to treatment.Objective: To evaluate efficacy and safety of two vitamin supplement regimenson Hcys serum levels over a 12 month period.Methods: We conducted a prospective, randomised, double-blind trial in 60 stableMHD patients (68 ± 13 years, 48% male, 50% diabetics). Patients were randomlyassigned to one of two treatment regimens: 1) daily renal multivitamin containingfolate (FA), vitamin B6 and B12 (5 mg, 10 mg and 0.4 mg respectively) (N= 27); and 2) supraphysiological daily doses (15 mg, 100 mg and 1 mg) (N = 33).These regimens were continued throughout the study period. Hcys levels werecompared with a control group from the general population (N = 276) matchedfor age and gender. Measurements: demographic and clinical data, serum levelsof Hcys, FA, B6, B12 at baseline and after 1, 3, 6 and 12 months of treatment;MTHFR gene polymorphism (PCRRT).Results: At baseline, global prevalence of hyperhomocysteinemia (tHcy �� 15µmol/L) was 100% in patients and 22% en controls. Hcys levels were significantlyhigher in patients versus controls (32.4 ± 8.9 vs 12.9 ± 6.8; P < 0,0001). Bothregimens were equally effective in reducing Hcys levels. As a whole, Hcys levelswere reduced by 23.6% (P < 0.001) after one month of treatment. The highest reductionwas observed at the sixth month (28.3%, 32.4 ± 8.9 vs 22.7 ± 6.4, P <0.001) and remained stable thereafter. However, only 12% of patients normalisedtheir plasma levels after 12 months of therapy. The effect of treatment was not influencedby age, gender, diabetes, body weight or time on MHD. Reduction rateof tHcy levels was related to baseline tHcy level (r = 0.500, P < 0.001) and baselineFA levels (r = -0.332, P = 0.009). The MTHFR polimorfism did not significantlymodified the effect of the treatment. No side effects were associated witheither regimen.Conclusions: Hyperhomocysteinemia is common in patients with conventionalHD schedules and this is not related to vitamin deficiencies. Vitamin supplementssignificantly reduce Hcys levels in a sustained but suboptimal way. Supraphysiologicaldoses did not improve the results. Further studies are requiered to demonstratethat this effect is associated with an improval in morbidity and mortality