Autor según el artículo: Balasubramanian R; Demler O; Guasch-Ferré M; Paynter NP; Sheehan R; Liu S; Manson JAE; Salas-Salvadó J; Martínez-Gonzalez M; Hu FB; Clish C; Rexrode KM

Departamento: Bioquímica i Biotecnologia

Autor/es de la URV: Salas Salvadó, Jorge

Palabras clave: Women Metabolome Medroxyprogesterone acetate Heart disease Estrogens Cardiovascular disease

Resumen: © 2020 Cambridge University Press. All rights reserved. Background: In the WHI-HT trials (Women's Health Initiative Hormone Therapy), treatment with oral conjugated equine estrogens and medroxyprogesterone acetate (CEE+MPA) resulted in increased risk of coronary heart disease (CHD), whereas oral conjugated equine estrogens (CEE) did not. Methods: Four hundred eighty-one metabolites were measured at baseline and at 1-year in 503 and 431 participants in the WHI CEE and CEE+MPA trials, respectively. The effects of randomized HT on the metabolite profiles at 1-year was evaluated in linear models adjusting for baseline metabolite levels, age, body mass index, race, incident CHD, prevalent hypertension, and diabetes. Metabolites with discordant effects by HT type were evaluated for association with incident CHD in 944 participants (472 CHD cases) in the WHI-OS (Women's Health Initiative Observational Study), with replication in an independent cohort of 980 men and women at high risk for cardiovascular disease. Results: HT effects on the metabolome were profound; 62% of metabolites significantly changed with randomized CEE and 52% with CEE+MPA (false discovery rate-Adjusted P value<0.05) in multivariable models. Concerted increases in abundance were seen within various metabolite classes including triacylglycerols, phosphatidylethanolamines, and phosphatidylcholines; decreases in abundance was observed for acylcarnitines, lysophosphatidylcholines, quaternary amines, and cholesteryl/cholesteryl esters. Twelve metabolites had discordant effects by HT type and were associated with incident CHD in the WHI-OS; a metabolite score estimated in a Least Absolute Shrinkage and Selection Operator regression was associated with CHD risk with an odds ratio of 1.47 per SD increase (95% CI, 1.27-1.70, P<10-6). All twelve metabolites were altered in the CHD protective direction by CEE treatment. One metabolite (lysine) was significantly altered in the direction of increased CHD risk by CEE+MPA; the remaining 11 metabolites were not significantly changed by CEE+MPA. The CHD associations of a subset of 4 metabolites including C58:11 triacylglycerol, C54:9 triacylglycerol, C36:1 phosphatidylcholine and sucrose replicated in an independent dataset of 980 participants in the PREDIMED trial (Prevención con Dieta Mediterránea). Conclusions: Randomized treatment with oral HT resulted in large metabolome shifts that generally favored CEE alone over CEE+MPA in term of CHD risk. Discordant metabolite effects between HT regimens may partially mediate the differences in CHD risk between the 2 WHI-HT trials.

Áreas temáticas: Genetics (clinical) Genetics & heredity Genetics Cardiology and cardiovascular medicine Cardiac & cardiovascular systems

Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/

Direcció de correo del autor: jordi.salas@urv.cat

Identificador del autor: 0000-0003-2700-7459

Fecha de alta del registro: 2023-02-19

Versión del articulo depositado: info:eu-repo/semantics/acceptedVersion

Enlace a la fuente original: https://www.ahajournals.org/doi/full/10.1161/CIRCGEN.119.002977

URL Documento de licencia: http://repositori.urv.cat/ca/proteccio-de-dades/

Referencia al articulo segun fuente origial: Circulation-Genomic And Precision Medicine. 13 (6): 618-629

Referencia de l'ítem segons les normes APA: Balasubramanian R; Demler O; Guasch-Ferré M; Paynter NP; Sheehan R; Liu S; Manson JAE; Salas-Salvadó J; Martínez-Gonzalez M; Hu FB; Clish C; Rexrode K (2020). Metabolomic Effects of Hormone Therapy and Associations with Coronary Heart Disease among Postmenopausal Women. Circulation-Genomic And Precision Medicine, 13(6), 618-629. DOI: 10.1161/CIRCGEN.119.002977

DOI del artículo: 10.1161/CIRCGEN.119.002977

Entidad: Universitat Rovira i Virgili

Año de publicación de la revista: 2020

Tipo de publicación: Journal Publications