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array:23 [ "pii" => "S0025775300711729" "issn" => "00257753" "doi" => "10.1016/S0025-7753(00)71172-9" "estado" => "S300" "fechaPublicacion" => "2000-01-01" "aid" => "71172" "copyright" => "Elsevier España, S.L.. Todos los derechos reservados" "copyrightAnyo" => "2000" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Med Clin. 2000;114:7-12" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1958 "formatos" => array:3 [ "EPUB" => 7 "HTML" => 1785 "PDF" => 166 ] ] "itemSiguiente" => array:18 [ "pii" => "S0025775300711730" "issn" => "00257753" "doi" => "10.1016/S0025-7753(00)71173-0" "estado" => "S300" "fechaPublicacion" => "2000-01-01" "aid" => "71173" "copyright" => "Elsevier España, S.L." "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Med Clin. 2000;114:13-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1209 "formatos" => array:3 [ "EPUB" => 10 "HTML" => 1062 "PDF" => 137 ] ] "es" => array:10 [ "idiomaDefecto" => true "titulo" => "Expresión fenotípica de la Lp(a) en niños y adolescentes españoles" "tienePdf" => "es" "tieneTextoCompleto" => 0 "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "13" "paginaFinal" => "15" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Phenotypic expressión of Lp(a) in Spanish children and adolescents" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Juan Antonio Gómez Gerique, Dolores López Martínez, Pilar Cancelas, María Teresa Montoya, María Dolores Gutiérrez, Amelia Porres" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Juan Antonio" "apellidos" => "Gómez Gerique" ] 1 => array:2 [ "nombre" => "Dolores" "apellidos" => "López Martínez" ] 2 => array:2 [ "nombre" => "Pilar" "apellidos" => "Cancelas" ] 3 => array:2 [ "nombre" => "María" "apellidos" => "Teresa Montoya" ] 4 => array:2 [ "nombre" => "María" "apellidos" => "Dolores Gutiérrez" ] 5 => array:2 [ "nombre" => "Amelia" "apellidos" => "Porres" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775300711730?idApp=UINPBA00004N" "url" => "/00257753/0000011400000001/v1_201307291354/S0025775300711730/v1_201307291354/es/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0025775300711717" "issn" => "00257753" "doi" => "10.1016/S0025-7753(00)71171-7" "estado" => "S300" "fechaPublicacion" => "2000-01-01" "aid" => "71171" "copyright" => "Elsevier España, S.L." "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Med Clin. 2000;114:3-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1411 "formatos" => array:3 [ "EPUB" => 11 "HTML" => 1274 "PDF" => 126 ] ] "es" => array:10 [ "idiomaDefecto" => true "titulo" => "Características clínicas de la artritis familiar en España. Estudio de 73 familias" "tienePdf" => "es" "tieneTextoCompleto" => 0 "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "3" "paginaFinal" => "6" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Clinical characteristics of familiar rheumatoid arthritis in Spain. A study of 73 families" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:2 [ 0 => array:2 [ "autoresLista" => "Alejandro Balsa, Juan Gijón" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Alejandro" "apellidos" => "Balsa" ] 1 => array:2 [ "nombre" => "Juan" "apellidos" => "Gijón" ] ] ] 1 => array:2 [ "autoresLista" => "Dora Pascual-Salcedo, Tomás Tinturé, María Victoria Irigoyen, Carlos Rodríguez-Lozano, Manuel Rodríguez" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Dora" "apellidos" => "Pascual-Salcedo" ] 1 => array:2 [ "nombre" => "Tomás" "apellidos" => "Tinturé" ] 2 => array:2 [ "nombre" => "María" "apellidos" => "Victoria Irigoyen" ] 3 => array:2 [ "nombre" => "Carlos" "apellidos" => "Rodríguez-Lozano" ] 4 => array:2 [ "nombre" => "Manuel" "apellidos" => "Rodríguez" ] 5 => array:1 [ "colaborador" => "Consorcio Español para la Artritis Reumatoide (CEAR)" ] 6 => array:1 [ "colaborador" => "European Consortium for Rheumatoid Arthritis Familiar (ECRAF)" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775300711717?idApp=UINPBA00004N" "url" => "/00257753/0000011400000001/v1_201307291354/S0025775300711717/v1_201307291354/es/main.assets" ] "es" => array:14 [ "idiomaDefecto" => true "titulo" => "Reducción de concentraciones elevadas de homocisteína con ácido fólico y vitaminas B en pacientes con tromboembolia venosa: relación entre respuesta y genotipo C677T de la metilén tetrahidrofólico reductasa (MTHFR)" "tieneTextoCompleto" => 0 "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "7" "paginaFinal" => "12" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Ángel José González Ordóñez, Jesús María Medina Rodríguez, Carmen Rosa Fernández Álvarez, Javier Sánchez García, José Manuel Fernández Carreira, María Victoria Álvarez Martínez, Eliecer Coto García" "autores" => array:7 [ 0 => array:4 [ "nombre" => "Ángel José" "apellidos" => "González Ordóñez" "email" => array:1 [ 0 => "jagonzalez@medynet.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff00010" ] 1 => array:2 [ "etiqueta" => "**" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Jesús María" "apellidos" => "Medina Rodríguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff00010" ] ] ] 2 => array:3 [ "nombre" => "Carmen Rosa" "apellidos" => "Fernández Álvarez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff00010" ] ] ] 3 => array:3 [ "nombre" => "Javier" "apellidos" => "Sánchez García" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff00010" ] ] ] 4 => array:3 [ "nombre" => "José Manuel" "apellidos" => "Fernández Carreira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff00015" ] ] ] 5 => array:3 [ "nombre" => "María Victoria" "apellidos" => "Álvarez Martínez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff00020" ] ] ] 6 => array:3 [ "nombre" => "Eliecer" "apellidos" => "Coto García" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff00020" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Hematología. Hospital San Agustín. Avilés" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff00010" ] 1 => array:3 [ "entidad" => "Unidad de Investigación. Hospital San Agustín. Avilés" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff00015" ] 2 => array:3 [ "entidad" => "Laboratorio de Genética Molecular. Hospital Central de Asturias. Oviedo" "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff00020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "**" "correspondencia" => "Correspondencia: Dr. A.J. González Ordóñez. Servicio de Hematología. Hospital San Agustín. 33400 Avilés. Asturias." ] ] ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Lowering high levels of fasting total homocysteine with folic acid and vitamins B in patients with venous thromboembolism: relationship between response and the C677T methylenetetrahydrofolate reductase (MTHFR) genotype" ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "1999-06-14" "fechaAceptado" => "1999-10-19" "PalabrasClave" => array:1 [ "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec220501" "palabras" => array:6 [ 0 => "Polimorfismo ADN" 1 => "Gen MTHFR" 2 => "Metilén tetrahidrofólico reductasa" 3 => "Trombosis venosa" 4 => "Homocisteína" 5 => "Ácido fólico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Fundamento</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Las concentraciones plasmaticas elevadas de homocisteina total (tHcy) se asocian con enfermedad trombotica arterial o venosa. Dependen principalmente del estado nutricional para el acido folico y vitaminas B<span class="elsevierStyleSup">12</span> o B<span class="elsevierStyleSup">6</span> pero tambien de la actividad enzimatica desarrollada por la metilen tetrahidrofolico reductasa (MTHFR). Evaluamos el grado de respuesta de la hiperhomocisteinemia (HHcy) a un sencillo esquema de suplementacion vitaminica respecto al genotipo de MTHFR.</p> <span class="elsevierStyleSectionTitle">Pacientes y metodos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se seleccionaron 227 pacientes, diagnosticados de tromboembolia venosa (TEV) y que fueron analizados para tHcy (ayunas) y para el polimorfismo genetico MTHFR-C677T. Cuando la tHcy excedio el limite normal (varones = 16 y mujeres = 15 μmol/l), los pacientes recibieron el equivalente a 1 mg de acido folico, 0,2 mg de vitamina B<span class="elsevierStyleSup">12</span> y 100 mg de vitamina B<span class="elsevierStyleSup">6</span>, diariamente durante 6 sema as. Posteriormente fueron reanalizados y la reduccion fue comparada por genotipos MTHFR, buscando cualquier diferencia en el grado de respuesta.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La tHcy media fue de 12,3 μmol/l (DE = 8). Los 51 pacientes hiperhomocisteinemicos (22%) tenian edad superior (65,1 anos) a los no-HHcy (55,0 anos) (p = 0,0001). La cumplimentacion del tratamiento fue apropiada en 46 pacientes (90%). La tHcy media pretratamiento fue de 23,2 μmol/l (DE = 10,5), y se redujo a 13,0 (DE = 5,9), el 42,1% (p = 0,0001). Por genotipos, los pacientes C/C de 21,0 a 13,2 μmol/l (37%) (n = 18), los C/T de 25,0 a 12,6 μmol/l (46%) (n = 24), y los homozigotos anormales T/T de 22,7 a 14,5 μmol/l (39%) (n = 4), aunque sin evidenciarse diferencias estadisticamente significativas. La respuesta fue completa (normalizandose la tHcy) en el 80% de los casos (37/46). Se observo una correlacion negativa (r = -0.471) (p = 0,005) entre edad y respuesta.</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El tratamiento con AF/B<span class="elsevierStyleSup">6</span>/B<span class="elsevierStyleSup">12</span> reduce en forma sencilla, rapida y eficaz (> 40% en 6 semanas) los valores patologicos de tHcy sin ninguna influencia del genotipo MTHFR. Dado que la HHcy parece relacionarse con las recidivas de trombosis venosa, parece prudente determinar la tHcy sistematicamente en pacientes con TEV, para intentar su reduccion en casos seleccionados.</p>" ] "en" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Background</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">High levels of plasma total homocysteine (tHcy) are involved in arterial or venous occlusive diseases. It esentially depends on the nutritional status of folic acid (FA) and vitamins B<span class="elsevierStyleSup">12</span> or B<span class="elsevierStyleSup">6</span>, but also on the methylenetetrahydrofolate reductase (MTHFR) enzymatic activity. We aim to evaluate the response of the hyperhomocysteinemia (HHcy) to a standard schedule of vitamin supplementation, according with the MTHFR genotype.</p> <span class="elsevierStyleSectionTitle">Patients and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">227 patients, diagnosed with venous thromboembolism (VTE) were analysed for tHcy (in fasting conditions), and for the MTHFR-C677T gene polymorphism. When the tHcy exceeded the cut off point (men = 16, women = 15 μmol/l), the patients were supplemented with a dose equivalent to 1 mg FA, 0.2 mg B<span class="elsevierStyleSup">12</span> and 100 mg of B<span class="elsevierStyleSup">6</span>, daily by 6 weeks. Afterwards they were reanalysed and the reduction was stratified by MTHFR genotype, looking for any difference in the response.</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The mean fasting tHcy was 12.3 μmol/l (SD = 8). The 51 hyperhomocysteinemic patients (22%) were older (65.1 y) than the normal ones (55.0 y) (p = 0.0001). The treatment was carried out properly in 46 patients (90%). The pre-treatment mean Hcy was 23.2 (SD = 10.5) μmol/l, and it was reduced to 13.0 (SD = 5.9) (p = 0.0001) (mean reduction = 42.1%). By genotype, the C/C reduced from 21.0 to 13.2 μmol/l (37%) (n = 18), the C/T from 25.0 to 12.6 μmol/l (46%) (n = 24), and the abnormal homozygotes T/T from 22.7 to 14.5 μmol/l (39%) (n = 4), although no statistical significant differences were found. In 80% of cases (37/46), tHcy values normalised. A negative correlation (r = –0.471) (p = 0.005) was observed between age and response.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The FA/B<span class="elsevierStyleSup">6</span>/B<span class="elsevierStyleSup">12</span> based therapy reduces in a simple, quick and effective way (> 40% in 6 weeks) the pathologic tHcy levels on a VTE population and this is not influenced by the MTHFR genotype. As HHcy seems related with recurrences of venous thrombosis, we could speculate if it would be useful to analyse routinely the tHcy, attempting reduction in selected cases.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "Referencias Bibliográficas" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:42 [ 0 => array:3 [ "identificador" => "bib00005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hyperhomocyst(e)inemia: a common and easily reversible risk factor for occlusive atherosclerosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.R. Malinow" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "1990" "volumen" => "81" "paginaInicial" => "2004" "paginaFinal" => "2006" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2188759" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib00010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Plasma homocysteine in venous thromboembolism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "L. Brattström" 1 => "L. Tengborn" 2 => "C. Lagerstedt" 3 => "B. Israelsson" 4 => "B. Hultberg" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Haemostasis" "fecha" => "1991" "volumen" => "21" "paginaInicial" => "51" "paginaFinal" => "57" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1864556" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib00015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High prevalence of hyperhomocyst(e)inemia in patients with juvenile venous thrombosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C.R. Falcon" 1 => "M. Cattaneo" 2 => "D. Panzeri" 3 => "I. Martinelli" 4 => "P.M. Mannucci" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arterioscler Thromb" "fecha" => "1994" "volumen" => "14" "paginaInicial" => "1080" "paginaFinal" => "1083" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8018663" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib00020" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of moderate hyperhomocysteinemia in patients with early-onset venous and arterial occlusive disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "I. Fermo" 1 => "S.V. D'Angelo" 2 => "R. Paroni" 3 => "G. Mazzola" 4 => "G. Calori" 5 => "A. D'Angelo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "1995" "volumen" => "123" "paginaInicial" => "747" "paginaFinal" => "753" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7574192" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib00025" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Is hyperhomocysteinemia a risk factor for recurrent venous thrombosis?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Den Heijer" 1 => "H.J. Blom" 2 => "W.B.J. Gerrits" 3 => "F.R. Rosendaal" 4 => "P.W. Wijermans" 5 => "G.M.J. Bos" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1995" "volumen" => "345" "paginaInicial" => "882" "paginaFinal" => "885" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7707810" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib00030" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hyperhomocysteinemia as a risk factor for deep-vein thrombosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Den Heijer" 1 => "T. Koster" 2 => "H.J. Blom" 3 => "G.M.J. Bos" 4 => "E. Briët" 5 => "P.H. Reitsma" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM199603213341203" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1996" "volumen" => "334" "paginaInicial" => "759" "paginaFinal" => "762" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8592549" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib00035" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hyperhomocysteinemia and deep-vein thrombosis: a case-control study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Simioni" 1 => "P. Prandoni" 2 => "A. Burlina" 3 => "D. Tormene" 4 => "C. Sardella" 5 => "V. Ferrari" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Thromb Haemost" "fecha" => "1996" "volumen" => "76" "paginaInicial" => "883" "paginaFinal" => "886" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8972005" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib00040" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin status and intake as primary determinants of homocysteinemia in elderly patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J. Selhub" 1 => "P.F. Jacques" 2 => "P.W.F. Wilson" 3 => "D. Rush" 4 => "I.H. Rosenberg" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "1993" "volumen" => "270" "paginaInicial" => "2693" "paginaFinal" => "2698" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8133587" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib00045" "etiqueta" => "9." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Frosst" 1 => "H.J. Bloom" 2 => "R. Milos" 3 => "P. Goyette" 4 => "C.A. Sheppard" 5 => "R.G. Matthews" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng0595-111" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "1995" "volumen" => "10" "paginaInicial" => "111" "paginaFinal" => "113" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7647779" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib00050" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S-S Kang" 1 => "J. Zhou" 2 => "P.W.K. Wong" 3 => "J. Kowalisyn" 4 => "G. Strokosch" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "1988" "volumen" => "43" "paginaInicial" => "414" "paginaFinal" => "421" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3177384" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib00055" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.F. Jacques" 1 => "A.G. Bostom" 2 => "R.R. Williams" 3 => "R.C. Ellison" 4 => "J.H. Eckfeldt" 5 => "I.H. Rosenberg" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "1996" "volumen" => "93" "paginaInicial" => "7" "paginaFinal" => "9" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8616944" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib00060" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial infarction in US physicians" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Ma" 1 => "M.J. Stampfer" 2 => "C.H. Hennekens" 3 => "P. Frosst" 4 => "J. Selhub" 5 => "J. Horsford" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "1996" "volumen" => "94" "paginaInicial" => "2410" "paginaFinal" => "2416" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8921781" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib00065" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Brattström L. Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "F. Landgren" 1 => "B. Israelsson" 2 => "A. Lindgren" 3 => "B. Hultberg" 4 => "A. Anderson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Intern Med" "fecha" => "1995" "volumen" => "237" "paginaInicial" => "381" "paginaFinal" => "388" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7714461" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib00070" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Homocysteine Lowering Trialists' Collaboration." "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Br Med J" "fecha" => "1998" "volumen" => "316" "paginaInicial" => "894" "paginaFinal" => "898" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib00075" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combined vitamin B<span class="elsevierStyleSup">6</span> and folic acid therapy in young patients arteriosclerosis and hyperhomocysteinemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Van der Berg" 1 => "D.G. Franken" 2 => "G.H.J. Boers" 3 => "H.J. Blom" 4 => "C. Jakobs" 5 => "C.D.A. Stehouwer" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Vasc Surg" "fecha" => "1994" "volumen" => "20" "paginaInicial" => "933" "paginaFinal" => "940" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7990188" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib00080" "etiqueta" => "16." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C.J. Boushey" 1 => "S.A.A. Beresford" 2 => "G.S. Omenn" 3 => "A.G. Motulsky" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "1995" "volumen" => "274" "paginaInicial" => "1049" "paginaFinal" => "1057" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7563456" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib00085" "etiqueta" => "17." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin requirements for the treatment of hyperhomocysteinemia in humans" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.B. Ubbink" 1 => "W.J.H. Vermaak" 2 => "A. Van der Merwe" 3 => "P.J. Becker" 4 => "R. Delport" 5 => "H.C. Potgieter" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Nutr" "fecha" => "1994" "volumen" => "10" "paginaInicial" => "1927" "paginaFinal" => "1933" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib00090" "etiqueta" => "18." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Total homocysteine in plasma or serum: methods and clinical applications" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "P.M. Ueland" 1 => "H. Refsum" 2 => "S.P. Stabler" 3 => "M.R. Malinow" 4 => "A. Andersson" 5 => "R.H. Allen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Chem" "fecha" => "1993" "volumen" => "39" "paginaInicial" => "1764" "paginaFinal" => "1779" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8375046" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib00095" "etiqueta" => "19." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hiperhomocisteinemia, un nuevo marcador de riesgo vascular: territorios vasculares afectados, papel en la patogénesis de la arterios-clerosis y la trombosis y tratamiento" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Córdoba Porras" 1 => "F. Blanco Vaca" 2 => "F. González Sastre" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Clin (Barc)" "fecha" => "1997" "volumen" => "109" "paginaInicial" => "715" "paginaFinal" => "725" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib000100" "etiqueta" => "20." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Concentraciones plasmáticas de homocisteína en pacientes con infarto cerebral isquémico" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "N. Vila" 1 => "R. Deulofeu" 2 => "A. Chamorro" 3 => "C. Piera" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Clin (Barc)" "fecha" => "1998" "volumen" => "110" "paginaInicial" => "605" "paginaFinal" => "608" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib000105" "etiqueta" => "21." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Moderate hyperhomocysteinemia is a highly prevalent defect in Spanish patients with venous thromboembolic disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Y. González" 1 => "J.C. Souto" 2 => "J. Mateo" 3 => "A. Córdoba" 4 => "F. Blanco-Vaca" 5 => "J. Fontcuberta" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Haematologica" "fecha" => "1998" "volumen" => "83" "paginaInicial" => "1126" "paginaFinal" => "1127" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9949633" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib000110" "etiqueta" => "22." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The VITA project: C677T mutation in methylenetetrahydrofolate reductase gene and risk of venous thromboembolism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Tosetto" 1 => "E. Missiaglia" 2 => "M. Frezzato" 3 => "F. Rodeghiero" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Br J Haematol" "fecha" => "1997" "volumen" => "97" "paginaInicial" => "804" "paginaFinal" => "806" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9217179" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib000115" "etiqueta" => "23." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thermolabile methylenetetrahydrofolate reductase and factor V Leiden in the risk of deep-vein thrombosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "L.A.J. Kluijtmans" 1 => "M. Den Heijver" 2 => "P.H. Reitsma" 3 => "S.G. Heil" 4 => "H.J. Blom" 5 => "F.R. Rosendaal" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Thromb Haemost" "fecha" => "1998" "volumen" => "79" "paginaInicial" => "254" "paginaFinal" => "258" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9493571" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib000120" "etiqueta" => "24." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic polymorphism of methylenetetrahydrofolate reductase and venous thromboembolism: a case-control study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.J. González-Ordóñez" 1 => "C.R. Fernández-Álvarez" 2 => "J.M. Medina-Rodríguez" 3 => "E. Coto" 4 => "M.V. Álvarez" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Haematologica" "fecha" => "1999" "volumen" => "84" "paginaInicial" => "190" "paginaFinal" => "191" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10091425" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib000125" "etiqueta" => "25." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The mutation Ala677 to Val in the methylenetetrahydrofolate reductase gene: a risk factor for arterial disease and venous thrombosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "V.R. Arruda" 1 => "P.M. Von Zuben" 2 => "L.C. Chiaparini" 3 => "J.M. Annichino-Bizzacchi" 4 => "F.F. Costa" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Thromb Haemost" "fecha" => "1997" "volumen" => "77" "paginaInicial" => "818" "paginaFinal" => "821" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9184384" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib000130" "etiqueta" => "26." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Low circulating folate and vitamin B<span class="elsevierStyleSup">6</span> concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease. European COMAC Group" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Robinson" 1 => "K. Arheart" 2 => "H. Refsum" 3 => "L. Brattström" 4 => "G. Boers" 5 => "P. Ueland" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "1998" "volumen" => "97" "paginaInicial" => "437" "paginaFinal" => "443" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9490237" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib000135" "etiqueta" => "27." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I.A. Brouwer" 1 => "M. Dusseldorp" 2 => "C.M. Thomas" 3 => "M. Duran" 4 => "J.G. Hautvast" 5 => "T.K. Eskes" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Clin Nutr" "fecha" => "1999" "volumen" => "69" "paginaInicial" => "99" "paginaFinal" => "104" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9925130" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib000140" "etiqueta" => "28." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Folate administration reduces circulating homocysteine levels in NIDDM patients on long-term metformin treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.K. Aarsand" 1 => "S.M. Carlsen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Intern Med" "fecha" => "1998" "volumen" => "244" "paginaInicial" => "169" "paginaFinal" => "174" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10095804" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib000145" "etiqueta" => "29." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Den Heijer" 1 => "I.A. Brouwer" 2 => "G.M.J. Bos" 3 => "H.J. Blom" 4 => "N.M. Van der Put" 5 => "A.P. Spaans" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Arterioscler Thromb Vascular Biol" "fecha" => "1998" "volumen" => "18" "paginaInicial" => "356" "paginaFinal" => "361" ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib000150" "etiqueta" => "30." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.R. Malinow" 1 => "P.B. Duell" 2 => "D.L. Hess" 3 => "P.H. Anderson" 4 => "W.D. Kruger" 5 => "B.E. Phillipson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM199804093381501" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1998" "volumen" => "338" "paginaInicial" => "1009" "paginaFinal" => "1015" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9535664" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib000155" "etiqueta" => "31." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effects of folic acid supplementation on plasma total homocysteine are modulated by multivitamin use and methylenetetrahydrofolate reductase genotypes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.R. Malinow" 1 => "F.J. Nieto" 2 => "W.D. Kruger" 3 => "P.B. Duell" 4 => "D.L. Hess" 5 => "R.A. Gluckman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arterioscler Thromb Vasc Biol" "fecha" => "1997" "volumen" => "17" "paginaInicial" => "1157" "paginaFinal" => "1162" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9194768" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib000160" "etiqueta" => "32." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effects of oral vitamin supplementation on cardiovascular risk factors" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.V. Woodside" 1 => "J.W.G. Yarnell" 2 => "I.S. Young" 3 => "E.E. McCrum" 4 => "C.C. Patterson" 5 => "F. Gey" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Proc Nutr Soc" "fecha" => "1997" "volumen" => "56" "paginaInicial" => "479" "paginaFinal" => "488" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9168555" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib000165" "etiqueta" => "33." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of vitamin B<span class="elsevierStyleSup">12</span>, folate and vitamin B<span class="elsevierStyleSup">6</span> supplements in elderly people with normal serum vitamin concentrations" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H.J. Naurath" 1 => "E. Joosten" 2 => "R. Riezler" 3 => "S.P. Stabler" 4 => "R.H. Allen" 5 => "J. Lindenbaum" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1995" "volumen" => "346" "paginaInicial" => "85" "paginaFinal" => "89" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7603218" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib000170" "etiqueta" => "34." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Unpredictable intra-individual variations in serum homocysteine levels on folic acid supplementation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C.R. Santhosh-Kumar" 1 => "J.C. Deutsch" 2 => "J.W. Ryder" 3 => "J.F. Kolhouse" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur J Clin Nutr" "fecha" => "1997" "volumen" => "51" "paginaInicial" => "188" "paginaFinal" => "192" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9076410" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib000175" "etiqueta" => "35." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I.M. Graham" 1 => "L.E. Daly" 2 => "H.M. Refsum" 3 => "K. Robinson" 4 => "L.E. Brattström" 5 => "P.M. Ueland" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "1997" "volumen" => "277" "paginaInicial" => "1775" "paginaFinal" => "1781" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9178790" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib000180" "etiqueta" => "36." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serum folate, homocysteine and colorectal cancer risk in women: a nested case-control study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I. Kato" 1 => "A.M. Dnistrian" 2 => "M. Schwartz" 3 => "P. Toniolo" 4 => "K. Koenig" 5 => "R.E. Shore" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.bjc.6690305" "Revista" => array:6 [ "tituloSerie" => "Br J Cancer" "fecha" => "1999" "volumen" => "79" "paginaInicial" => "1917" "paginaFinal" => "1922" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10206314" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib000185" "etiqueta" => "37." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prospective blinded study of the relationship between plasma homocysteine and progression of asymptomatic peripheral arterial disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.r. Taylor LM" 1 => "G.L. Moneta" 2 => "G.J. Sexton" 3 => "R.A. Schuff" 4 => "J.M. Porter" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Vasc Surg" "fecha" => "1999" "volumen" => "29" "paginaInicial" => "8" "paginaFinal" => "21" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9925456" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib000190" "etiqueta" => "38." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Plasma homocysteine levels and mortality in patients with coronary artery disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "O. Nygard" 1 => "E. Nordrehaug" 2 => "H. Refsum" 3 => "P.M. Ueland" 4 => "M. Farstad" 5 => "S.E. Vollset" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM199707243370403" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1997" "volumen" => "337" "paginaInicial" => "230" "paginaFinal" => "236" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9227928" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib000195" "etiqueta" => "39." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A common methylenetetrahydrofolate reductase gene and longevity" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Brattstrom" 1 => "Y. Zhang" 2 => "M. Hurtig" 3 => "H. Refsum" 4 => "S. Ostensson" 5 => "L. Fransson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Atherosclerosis" "fecha" => "1998" "volumen" => "141" "paginaInicial" => "315" "paginaFinal" => "319" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9862180" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib000200" "etiqueta" => "40." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Determinants and vitamin responsiveness of intermediate hyperhomocysteinemia (> or = 40 micromol/liter). The Hordaland Homocysteine Study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.B. Guttormsen" 1 => "P.M. Ucland" 2 => "I. Nesthus" 3 => "O. NygArd" 4 => "J. Schneede" 5 => "S.E. Vollset" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI119024" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "1996" "volumen" => "98" "paginaInicial" => "2174" "paginaFinal" => "2183" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8903338" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib000205" "etiqueta" => "41." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Major lifestyle determinants of plasma total homocysteine distribution: the Hordaland Homocysteine Study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "O. NygArd" 1 => "H. Refsum" 2 => "P.M. Ucland" 3 => "S.E. Vollset" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Clin Nutr" "fecha" => "1998" "volumen" => "67" "paginaInicial" => "263" "paginaFinal" => "270" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9459374" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib000210" "etiqueta" => "42." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hyperhomocysteinemia is a risk factor of recurrent venous thromboembolism" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Eichinger" 1 => "A. Stümpflen" 2 => "M. Hirschl" 3 => "C. Blalonczyk" 4 => "K. Herkner" 5 => "M. Stain" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Thromb Haemost" "fecha" => "1998" "volumen" => "80" "paginaInicial" => "566" "paginaFinal" => "569" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9798970" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "es" "url" => "/00257753/0000011400000001/v1_201307291354/S0025775300711729/v1_201307291354/es/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/00257753/0000011400000001/v1_201307291354/S0025775300711729/v1_201307291354/es/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775300711729?idApp=UINPBA00004N" ]
