La puntuación de riesgo poligénico identifica el subgrupo con mayor carga de aterosclerosis y mayor beneficio relativo de la terapia con estatinas en el entorno de prevención primaria

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Pradeep Natarajan¹, Robin Young¹, Nathan O Stitziel¹

¹From Center for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital, Boston (P.N., S.K.); Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge (P.N., S.K.); Department of Medicine, Harvard Medical School, Boston, MA (P.N., S.K.); Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, United Kingdom (R.Y., A.B.); Division of Statistical Genetics, Department of Genetics, Cardiovascular Division, Department of Medicine, and McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO (N.O.S.); British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences (S.P., N.S.), and Robertson Centre for Biostatistics (I.F.), University of Glasgow, United Kingdom; Generation Scotland, Centre for Genomic and Experimental Medicine, University of Edinburgh, United Kingdom (S.P.); Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (U.B., R.M., S.S., V.F.); Genetics and Pharmacogenomics Department, Merck Sharpe & Dohme Corp, Boston, MA (D.F.R.); and Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia (D.J.R.).

|February 23, 2017

Resumen

Las personas con alto riesgo genético de enfermedad cardíaca se benefician más del tratamiento con estatinas. Esta terapia reduce significativamente el riesgo de eventos cardiovasculares en individuos de alto riesgo, mostrando una mayor eficacia que en la población general.

Área de la Ciencia:

Medicina cardiovascular
La genética
Farmacología

Sus antecedentes:

La terapia con estatinas reduce consistentemente el riesgo cardiovascular en diversas poblaciones.
Los ensayos previos sugieren una mayor eficacia de las estatinas en individuos con alta predisposición genética a la enfermedad cardíaca.
Este estudio tuvo como objetivo validar esta observación en un ensayo de prevención primaria y evaluar la carga subclínica de la aterosclerosis.

Objetivo del estudio:

Confirmar una mayor reducción del riesgo relativo de la terapia con estatinas en individuos de alto riesgo genético dentro de un ensayo de prevención primaria.
Investigar la asociación entre las puntuaciones de riesgo genético y la aterosclerosis subclínica.
Comparar la eficacia del tratamiento con estatinas en poblaciones de alto riesgo genético frente a poblaciones de riesgo genético promedio.

Principales métodos:

Se utilizaron datos del Estudio de Prevención Coronaria del Oeste de Escocia (WOSCOPS), el Desarrollo del Riesgo de la Arteria Coronaria en Adultos Jóvenes (CARDIA) y los estudios BioImage.
Las puntuaciones de riesgo poligénico calculadas (PRS) basadas en las variantes comunes de la secuencia de ADN asociadas con la enfermedad coronaria.
Comparó la eficacia relativa del tratamiento con estatinas en individuos con alta PRS frente a otros y evaluó la asociación de PRS con la calcificación de la arteria coronaria y la placa carotídea.

Principales resultados:

En WOSCOPS, los individuos de alto riesgo genético mostraron una reducción del riesgo relativo del 44% con estatinas frente al 24% en otros.
El metanálisis en tres ensayos reveló una reducción del riesgo relativo del 46% en individuos de alto riesgo genético frente al 26% en otros.
Un PRS más alto se correlacionó con una mayor probabilidad de calcificación de la arteria coronaria y carga de placa carotídea.

Conclusiones:

Los individuos de alto riesgo genético presentan una mayor aterosclerosis subclínica.
Estas personas obtienen beneficios superiores relativos y absolutos del tratamiento con estatinas para prevenir los eventos iniciales de enfermedad coronaria.

Palabras clave:

los humanos Inhibidores de la hidroximetilglutaril-CoA reductasa Polimorfismo genético la prevención primaria Calcificación vascular

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