Metaanálisis2021Financiado por la industriaVínculos de autores con la industriaAcceso abierto

Financiado en parte por Biogen

Cholesteryl ester transfer protein (CETP) as a drug target for cardiovascular disease

Schmidt AF, Hunt NB, Gordillo-Marañón M, Charoen P, Drenos F, Kivimaki M, Lawlor DA, Giambartolomei C, Papacosta O, Chaturvedi N, Bis JC, O'Donnell CJ, Wannamethee G, Wong A, Price JF, Hughes AD, Gaunt TR, Franceschini N, Mook-Kanamori DO, Zwierzyna M, Sofat R, Hingorani AD, Finan C

Nature communications · 115 citas

Etiquetas de revisión

Vínculos de autores con la industriaFinanciado por la industria

Datos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.

Cómo se estudió

Diseño: Metaanálisis (indexado por PubMed)
Estudiado en: Personas
Resultado principal: Eventos clínicos como enfermedad o muerte

Quién lo pagó

Financiación: Financiado por la industria
Empresa: Biogen
Organización sin fines de lucro: Wellcome Trust
Gobierno: Scottish Government
Gobierno: UK Research and Innovation
Organización sin fines de lucro: Cancer Research UK
Gobierno: National Institute for Health and Care Research
Organización sin fines de lucro: British Heart Foundation
Universidad u hospital: University College London
Organización sin fines de lucro: Rosetrees Trust
Universidad u hospital: University of Bristol
Gobierno: ZonMw
Gobierno: Academy of Finland
Gobierno: Northwest Regional Development Agency
Gobierno: Thailand Research Fund
Gobierno: National Institutes of Health
Gobierno: Medical Research Council
Gobierno: National Institute on Aging
Gobierno: National Heart, Lung, and Blood Institute
Gobierno: National Institute of Diabetes and Digestive and Kidney Diseases
Gobierno: U.S. National Library of Medicine
Gobierno: National Institute on Minority Health and Health Disparities
Gobierno: NIDDK NIH HHS
Gobierno: NLM NIH HHS
Gobierno: NHLBI NIH HHS
Gobierno: NIA NIH HHS
Organización sin fines de lucro: Rosetrees
Gobierno: NIMHD NIH HHS
Gobierno: National Institute for Health Research (NIHR)
Autores: Al menos un autor declara un vínculo económico con la industria
Subvenciones: Wellcome Trust (MR/S011676/1); Medical Research Council ([MC_UU_12019/1); British Heart Foundation (CH/F/20/90003); University of Bristol (MC_UU_00011/4); National Institute for Health and Care Research (NF‐0616‐10102); UK Research and Innovation (MR/S011676); British Heart Foundation (FS/17/70/33482D); Medical Research Council (MC_UU_00011/6); Thailand Research Fund (MRG6280088); Wellcome Trust (NF-0616-10102); Wellcome Trust (MR/R024227/1); National Heart, Lung, and Blood Institute (MR/R024227); British Heart Foundation (NF-0616-10102); Medical Research Council (S011676); Wellcome Trust (S011676); Medical Research Council (MR/R024227); National Institute on Aging (RF1AG062553); Medical Research Council (V033867); U.S. National Library of Medicine (R01LM010098); Medical Research Council (RG/10/12/28456); Medical Research Council (MC_UU_00011/4); British Heart Foundation (MR/S011676/1); National Heart, Lung, and Blood Institute (MR/R024227/1); Wellcome Trust (R024227); Wellcome Trust (MC_UU_00011/6); Cancer Research UK (29019); Medical Research Council (NF-0616-10102); Medical Research Council (MR/S011676/1); National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK117445); National Heart, Lung, and Blood Institute (R21-HL140385); Academy of Finland (311492); Medical Research Council (R024227); British Heart Foundation (MR/S011676); National Institutes of Health (1rf1ag062553-01); National Institute for Health and Care Research (MR/V033867/1); Rosetrees Trust (M202-F2); Wellcome Trust (MC_UU_00011/4); Medical Research Council (MR/S011676); Medical Research Council (MR/R024227/1); British Heart Foundation (MC_UU_00011/6); University of Bristol (MR/S011676/1); British Heart Foundation (FS/17/70/33482); Medical Research Council (MR/R024227/1); Medical Research Council (AA/18/7/34219); Medical Research Council (MR/S011676/1); National Heart, Lung, and Blood Institute (R01 HL105756); National Institute for Health and Care Research (311492); Wellcome Trust (221854); Wellcome Trust (MR/R024227); British Heart Foundation (AA/18/6/34223); Wellcome Trust (221854/Z/20/Z); British Heart Foundation (RG/10/12/28456); National Heart, Lung, and Blood Institute (HL140385); University of Bristol (MC_UU_00011/6); Wellcome Trust (CH/F/20/90003); Academy of Finland (MR/S011676); Medical Research Council (MR/V033867/1); British Heart Foundation (PG/18/50/33837); UK Research and Innovation (R024227); British Heart Foundation (AA/18/7/34219); Medical Research Council (S011676/1); Medical Research Council (R024227/1); Academy of Finland (R024227); ZonMw (91614023); National Institute on Aging (R01AG025533); Medical Research Council (CH/F/20/90003); Wellcome Trust (AA/18/7/34219); British Heart Foundation (R024227); Medical Research Council (MC_UU_00011/4); ZonMw (VENI Grant 916.14.023); University of Bristol (CH/F/20/90003); National Institute on Minority Health and Health Disparities (R01MD012765); University of Bristol (MC_UU_12019/1); UK Research and Innovation (MR/V033867/1); British Heart Foundation (MR/R024227/1); Medical Research Council (311492); National Institutes of Health (MR/R024227); UK Research and Innovation (311492); National Institutes of Health (S011676); Medical Research Council (MC_UU_00011/6); National Institute for Health and Care Research (MC_UU_00011/6); National Institute for Health and Care Research (NIHR202383); National Institute for Health and Care Research (MC_UU_00011/4); Wellcome Trust (311492); British Heart Foundation (CS/13/1/30327); National Institute for Health and Care Research (MR/S011676); British Heart Foundation (Accelerator AA/18/6/34223); National Institutes of Health (R024227); University of Bristol (AA/18/7/34219); Medical Research Council (MC_UU_00011); National Institute for Health and Care Research (R024227); British Heart Foundation (SP/13/6/30554); British Heart Foundation (MR/R024227); National Institutes of Health (R01-LM010098); National Institutes of Health (LM010098); British Heart Foundation (311492)

Según 28 financiadores declarados y la declaración de financiación del texto completo.

Publicación

Publicado: 2021-09-24 · Nat Commun · vol. 12 · número 1 · pág. 5640
Editorial: Nature Portfolio
Citado: 142 citas · más que el 100% de estudios similares · 20.1× el promedio de su campo
Impacto: Entre el 10 % más citado de su campo
Referencias: 73 trabajos
Acceso: Acceso abierto (revista) · CC-BY
Áreas de investigación: Lipoproteins and Cardiovascular Health · Genetic Associations and Epidemiology · Paraoxonase enzyme and polymorphisms
Palabras clave: cholesteryl ester transfer protein, CETP inhibitors, coronary artery disease, PCSK9, Mendelian randomization, cardiovascular risk, age-related macular degeneration, lipoprotein metabolism, heart failure, chronic kidney disease, Alzheimer's disease, stroke, atrial fibrillation
MeSH: humans, cardiovascular diseases, coronary disease, amides, esters, sulfhydryl compounds, oxazolidinones, benzodiazepines, quinolines, anticholesteremic agents, cholesterol ester transfer proteins, mendelian randomization analysis

DOI ↗PubMed Central ↗OpenAlex ↗

24 autores

Amand Floriaan Schmidt🇳🇱🇬🇧 · autor de correspondenciaUniversity Medical Center Utrecht; British Heart Foundation; University College London
Nicholas B. Hunt🇳🇱Utrecht University
María Gordillo‐Marañón🇬🇧British Heart Foundation; University College London
Pimphen Charoen🇹🇭🇬🇧Mahidol University; University College London
Fotios Drenos🇬🇧University College London; Brunel University of London
Juan Pablo Casas🇺🇸🇬🇧Brigham and Women's Hospital; Harvard University; VA Boston Healthcare System; University College London
Mika Kivimaki B🇬🇧University of Bristol; NIHR Bristol Biomedical Research Centre; MRC Integrative Epidemiology Unit; University College London
Debbie A. Lawlor🇮🇹🇬🇧Italian Institute of Technology; University of Bristol; NIHR Bristol Biomedical Research Centre; MRC Integrative Epidemiology Unit
Claudia Giambartolomei🇺🇸🇮🇹🇬🇧University of California, Los Angeles; Italian Institute of Technology; University College London
Olia Papacosta🇬🇧University College London
Nish Chaturvedi🇺🇸🇬🇧University of Washington; University College London
Joshua C. Bis🇺🇸Brigham and Women's Hospital; Harvard University; University of Washington; VA Boston Healthcare System
Christopher J. O’Donnell🇺🇸🇬🇧VA Boston Healthcare System; University College London
S. Goya Wannamethee🇬🇧MRC Unit for Lifelong Health and Ageing; University College London
Andrew Wong🇬🇧MRC Unit for Lifelong Health and Ageing; University of Edinburgh
Jackie F. Price🇬🇧MRC Unit for Lifelong Health and Ageing; University College London; University of Edinburgh
Alun David Hughes🇬🇧University of Bristol; NIHR Bristol Biomedical Research Centre; MRC Unit for Lifelong Health and Ageing; MRC Integrative Epidemiology Unit; University College London
Tom R. Gaunt🇺🇸🇬🇧University of North Carolina at Chapel Hill; University of Bristol; NIHR Bristol Biomedical Research Centre; MRC Integrative Epidemiology Unit
Nora Franceschini🇺🇸🇳🇱University of North Carolina at Chapel Hill; Leiden University Medical Center
Dennis O Mook-Kanamori🇳🇱🇬🇧Leiden University Medical Center; University College London
Magdalena Zwierzyna🇬🇧British Heart Foundation; University College London
Reecha Sofat🇬🇧Health Data Research UK; University College London
Aroon Dinesh Hingorani🇳🇱🇬🇧University Medical Center Utrecht; British Heart Foundation; Health Data Research UK; University College London
Chris Finan🇳🇱🇬🇧University Medical Center Utrecht; British Heart Foundation; University College London

Resumen

El texto original del estudio, en el idioma en que se publicó.

Development of cholesteryl ester transfer protein (CETP) inhibitors for coronary heart disease (CHD) has yet to deliver licensed medicines. To distinguish compound from drug target failure, we compared evidence from clinical trials and drug target Mendelian randomization of CETP protein concentration, comparing this to Mendelian randomization of proprotein convertase subtilisin/kexin type 9 (PCSK9). We show that previous failures of CETP inhibitors are likely compound related, as illustrated by significant degrees of between-compound heterogeneity in effects on lipids, blood pressure, and clinical outcomes observed in trials. On-target CETP inhibition, assessed through Mendelian randomization, is expected to reduce the risk of CHD, heart failure, diabetes, and chronic kidney disease, while increasing the risk of age-related macular degeneration. In contrast, lower PCSK9 concentration is anticipated to decrease the risk of CHD, heart failure, atrial fibrillation, chronic kidney disease, multiple sclerosis, and stroke, while potentially increasing the risk of Alzheimer's disease and asthma. Due to distinct effects on lipoprotein metabolite profiles, joint inhibition of CETP and PCSK9 may provide added benefit. In conclusion, we provide genetic evidence that CETP is an effective target for CHD prevention but with a potential on-target adverse effect on age-related macular degeneration.

Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).

Leer el texto completo ↗Ver en PubMed ↗

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