Ateromatosis subclínica y otros factores de riesgo cardiovascular en pacientes con psoriasis

  1. Castellote Caballero, Luisa
Dirigida por:
  1. Salvador Arias Santiago Director/a
  2. Cristina Campoy Folgoso Codirector/a
  3. M. Yolanda Castellote Caballero Codirectora

Universidad de defensa: Universidad de Granada

Fecha de defensa: 27 de septiembre de 2017

Tribunal:
  1. Agustín Buendia Eisman Presidente/a
  2. Francisco Javier Gómez Jiménez Secretario/a
  3. J. Jiménez Jáimez Vocal
  4. Miguel Ángel Arrabal Polo Vocal
  5. María del Carmen Cano García Vocal

Tipo: Tesis

Resumen

RESUMEN INTRODUCCION La psoriasis es una enfermedad sistémica, crónica que lleva consigo una inflamación y mayor riesgo cardiovascular. Fisiopatológicamente consiste en un disbalance de la expresión inmune predominando una respuesta Th1 y una elevación de las concentraciones séricas de citoquinas. Con este estudio se pretende realizar un acercamiento al estudio de la psoriasis como enfermedad sistémica y sus comorbilidades asociadas así como demostrar su asociación con los eventos cardiovasculares y la disfunción endotelial. Destacantdo el papel de los métodos de imagen para realizar el diagnostico precoz de la disfunción endotelial y la ateromatosis en fase subclínica. OBJETIVOS DEL ESTUDIO Estudiar la prevalencia de la ateromatosis subclínica y la disfunción endotelial en pacientes con psoriasis respecto del grupo control. El estudio del GIM carotideo y la prevalencia de placa de ateroma en pacientes con psoriasis en relación al grupo control. Relacionar la presencia de placa de ateroma y otros factores de riesgo cardiovascular clínicos (síndrome metabólico) en pacientes con psoriasis. Analizar qué mecanismos patogénicos pueden explicar la asociación de citoquinas proinflamatorias y clusterinas. La relación entre los niveles de clusterinas con la ateromatosis subclínica carotidea en pacientes con psoriasis. La modificación del grosor íntima media en pacientes con psoriasis tras realizar una intervención farmacológica durante 9 meses con atorvastatina 40 mg. Medir la disfunción endotelial mediante estudios de ultrasonografía braquial en pacientes con psoriasis en relación al grupo control. METODOLOGIA Se trata de un estudio observacional transversal de casos y controles. Los pacientes incluidos en el estudio han sido diagnosticados de psoriasis y pertenecen al Hospital Universitario san Cecilio y Hospital Virgen de las Nieves de Granada entre enero de 2011 a mayo de 2014. La valoración de la ateromatosis se realizo mediante ecografía Doppler .Tanto para medir el GIM en arterias carótidas comunes como para medir la diferencia de volumen en la arteria braquial como respuesta a la interrupción de flujo, como medida indirecta de disfunción endotelial. Realizamos una medición de clusterina, MIF y citoquinas . El plasma se aisló mediante centrifugación en gradiente de Ficoll y las alícuotas se guardaron a -80ºC hasta la realización de los análisis que se llevaron a cabo en el Instituto de Parasitología y Biomedicina López Neyra de Granada. Las concentraciones plasmáticas de clusterina y MIF en pacientes y controles se midió por ELISA. El procedimiento analítico se realizó por duplicado para ello se utilizaron los ensayos de ELISA correspondientes (Nº RD194034200R; BioVendor, Brno, Czech Republic y Nº DMF00B; R&D System, Abingdon, UK, para Clusterina y para MIF, respectivamente) siguiendo las instrucciones de los fabricantes. La determinación de las citoquinas se realizó mediante el kit BioPlex precisión proHuman Cytokine 10 plex que determina de forma simultánea las siguientes citoquinas: IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 (p70), IL-13, IFN-γ and TNF-α. Se siguieron los protocolos que proporciona el fabricante (Bio-Rad). CONCLUSIONES 1. El GIM medido en las arterias carótidas comunes en los pacientes con psoriasis, presentó un valor significativamente superior a los controles y en la distribución por sexo fue en los varones donde este valor fue superior.Los pacientes con psoriasis presentaron una prevalencia de placa de ateroma carotidea significativamente superior al grupo control. 2. Los pacientes con placas de ateroma, presentaros niveles superiores de insulina, obesidad abdominal, presión arterial y niveles inferiores de c-HDL, mostrando una asociación entre los parámetros del síndrome metabólico con la ateromatosis carotidea. 3. Los pacientes con psoriasis y placa de ateroma presentaron valores significativamente superiores de citoquinas proinflamatorias como IL-1, IL2, IL6, IL10, IL12, IL13 y TNF, por lo que podrían tener una utilidad como biomarcadores. 4. Los pacientes con psoriasis mostraron valores significativamente inferiores de clusterina y superiores de MIF en relación con los controles.Los sujetos con psoriasis y placa de ateroma presentaron niveles superiores de MIF. 5. Tras el tratamiento con atorvastatina 40 mgdurante 9 meses en un subgrupo de pacientes con psoriasis y dislipemia, se observó una disminución leve del GIM. 6. Los pacientes con psoriasis presentan un incremento del riesgo cardiovascular y ateromatosis carotidea subclínica por lo que podrían beneficiarse de un diagnostico y tratamiento precoz. 9. BIBLIOGRAFIA 1. A Bertomeu Ruiz, D. Zambón Rados. Med Integrd 2002;40:394-405. 2. Aksu F1, Caliskan M, Keles N et al. 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