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~~~~~~~~~~~~~~~~  P   );  P+sZCU 4  3@)$=c6N3!Rl +; M.+ - =3!a a      a  $" &r<dH  5$'?98\ <s#   :~L / S   T ,>+ "!I,#       <-#F7   ;;CZy %&m#q'(e> *+hb$s#ڿE`"  b$$>I$ b$-gB4nyө* "$ˏqv[9t$b$n0$"$;W[-La4"$Qq_}yNqUP"$ҷbPs_Pm2$thIx<R$"$>hx=_Wk$"$zCU>hx j n0e0e     A5% 8c8c     ?A)BCD|E||S" @> ʚ;>7ʚ;g4BdBdv 0(pp<4!d!d` 0L62<4dddd` 0L62 <4dddd 0Lg4=d=dv 0.p po___PPT9%hlpL.R;S;X;\;`;z? %O =0UBEl cido flico a largo plazo es eficaz para la prevencin del AVCCC,fff  AntecedentesLos niveles elevados de homocistena son un factor de riesgo independiente de: cardiopata isqumica, AVC y trombosis venosa profunda. Desde 1998, los derivados de los cereales en EEUU y en Canad se han complementado con cido flico con la finalidad de prevenir estas enfermedades a travs de este mecanismo. Sin embargo, la eficacia de los tratamientos que disminuyen estos niveles es controvertida. BOZ;ZZO; t  ObjetivosRevisar sistemticamente la literatura para estimar la eficacia de los complementos de cido flico para la prevencin de los AVC.  Diseo (1)Metaanlisis. Para localizar los estudios de inters: se llev a cabo una bsqueda en MEDLINE sin restriccin de idioma de publicacin y se consult con expertos sobre el tema. Criterios de inclusin: ensayos clnicos, que especificaban el nmero de eventos en el grupo intervencin y en el grupo control y ste era >10, en los que la intervencin consista en complementos de cido flico (con o sin vitamina B) y la duracin de la misma erae"6 meses.\6Z}ZZZ6}  Diseo (2)Variable de resultado principal: riesgo relativo de AVC. Se llev a cabo un anlisis estratificado por: duracin del tratamiento, reduccin en la concentracin de homocistena conseguida, y presencia previa de complementos de cido flico en los cereales. *ii SResultados (1) Resultados (2)$En todos se incluan personas con enfermedades preexistentes como: antecedentes de AVC o de cardiopata isqumica. Duracin de la intervencin: 24-72 meses. 3 estudios se llevaron a cabo en reas donde se complementaban los cereales con cido flico. Las concentraciones medias de homocistena de los diferentes estudios variaron entre 12,1 y 35,0 mol/L. Cuando se analizaron todos los estudios en su conjunto, la utilizacin de cido flico produjo una reduccin del riesgo de AVC del 18% (RR 0,82; IC95% 0,68 1,00; P=0045).<C2C2, 8 Resultados (3)T ConclusionesXLos autores concluyen que el cido flico es eficaz para la prevencin primaria del AVC.gComentario (1)wHace ms de 20 aos que algunos autores propusieron que los valores elevados de homocistena en plasma podan contribuir a aumentar el riesgo de aterosclerosis. Desde entonces, se han llevado a cabo varios estudios longitudinales que han demostrado que la hiperhomocistinemia es un factor de riesgo independiente de: AVC, cardiopata isqumica y trombosis venosa profunda..>Z:Z>:,O dTComentario (2)~Los principales determinantes de las concentraciones de homcistena en sangre son: el aporte diettico de metionina (el aminocido de que procede), los factores genticos y el aporte diettico de cido flico, vitamina B12 y, en menor medida, vitamina B6. Las principales fuentes de cido flico son: las verduras de hoja verde, las legumbres, los frutos secos y las naranjas.S0 d0 d-0 dO0 dS  -Ob7 ' !S|rComentario (3)La medida ms econmica para disminuir la homocistinemia es la administracin de suplementos de cido flico. A dosis de 1-5 mg/d reduce las concentraciones de homocistena en un 25%. Tiene el inconveniente de que antes de iniciar el tratamiento hay que medir el nivel de vitamina B12, ya que el tratamiento con cido flico podra enmascarar las manifestaciones hemtalgicas de un dficit de cobalamina y, por lo tanto, aumentar el riesgo de aparicin de lesiones neurolgicas. 00 d b)E   MComentario (4) Pese a todo, algunos pases entre los que se encuentran EEUU y Canad han optado por reforzar sus cereales con cido flico. Sin embargo, los ensayos clnicos sobre el efecto de los suplementos de cido flico sobre las enfermedades cardiovasculares han mostrado efectos contradictorios. Un metaanlisis publicado el ao pasado no encontr que redujese el riesgo las enfermedades cardiovasculares ni la mortalidad total. El riesgo relativo observado para los AVC fue de 0,84, pero no alcanz la significacin estadstica. 0 Z$ Comentario (5)La reduccin del riesgo de AVC observada en este metaanlisis fue similar, pero en este caso fue estadsticamente significativa. Los autores explican la diferencia entre sus resultados y los de anlisis previos en que: varios de estos se haban llevado a cabo en pases que ya reforzaban sus cereales, en los que suplementos adicionales no tenan ningn efecto otros se haban llevado a cabo en pacientes con enfermedad cerebrovascular previa, en los que tampoco se apreci ningn efecto beneficioso. Apoyan la eficacia del tratamiento que se haya detectado una relacin dosis-respuesta en relacin con: la duracin del tratamiento y la reduccin de la homocisteinemia conseguida. \ZZgZOZgO>0 h/3456> ? 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