Cargando…

Short-term changes in klotho and FGF23 in heart failure with reduced ejection fraction—a substudy of the DAPA-VO(2) study

The klotho and fibroblast growth factor 23 (FGF-23) pathway is implicated in cardiovascular pathophysiology. This substudy aimed to assess the changes in klotho and FGF-23 levels 1-month after dapagliflozin in patients with stable heart failure and reduced ejection fraction (HFrEF). The study includ...

Descripción completa

Detalles Bibliográficos
Autores principales: Mora-Fernández, Carmen, Pérez, Adora, Mollar, Anna, Palau, Patricia, Amiguet, Martina, de la Espriella, Rafael, Sanchis, Juan, Górriz, Jose Luis, Soler, María José, Navarro-González, Juan F., Núñez, Julio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10515719/
https://www.ncbi.nlm.nih.gov/pubmed/37745119
http://dx.doi.org/10.3389/fcvm.2023.1242108
_version_ 1785109008377446400
author Mora-Fernández, Carmen
Pérez, Adora
Mollar, Anna
Palau, Patricia
Amiguet, Martina
de la Espriella, Rafael
Sanchis, Juan
Górriz, Jose Luis
Soler, María José
Navarro-González, Juan F.
Núñez, Julio
author_facet Mora-Fernández, Carmen
Pérez, Adora
Mollar, Anna
Palau, Patricia
Amiguet, Martina
de la Espriella, Rafael
Sanchis, Juan
Górriz, Jose Luis
Soler, María José
Navarro-González, Juan F.
Núñez, Julio
author_sort Mora-Fernández, Carmen
collection PubMed
description The klotho and fibroblast growth factor 23 (FGF-23) pathway is implicated in cardiovascular pathophysiology. This substudy aimed to assess the changes in klotho and FGF-23 levels 1-month after dapagliflozin in patients with stable heart failure and reduced ejection fraction (HFrEF). The study included 29 patients (32.2% of the total), with 14 assigned to the placebo group and 15 to the dapagliflozin, as part of the double-blind, randomized clinical trial [DAPA-VO(2) (NCT04197635)]. Blood samples were collected at baseline and after 30 days, and Klotho and FGF-23 levels were measured using ELISA Kits. Between-treatment changes (raw data) were analyzed by using the Mann-Whitney test and expressed as median (p25%–p75%). Linear regression models were utilized to analyze changes in the logarithm (log) of klotho and FGF-23. The median age was 68.3 years (60.8–72.1), with 79.3% male and 81.5% classified as NYHA II. The baseline medians of left ventricular ejection fraction, glomerular filtration rate, NT-proBNP, klotho, and FGF-23 were 35.8% (30.5–37.8), 67.4 ml/min/1.73 m(2) (50.7–82.8), 1,285 pg/ml (898–2,305), 623.4 pg/ml (533.5–736.6), and 72.6 RU/ml (62.6–96.1), respectively. The baseline mean peak oxygen uptake was 13.1 ± 4.0 ml/kg/min. Compared to placebo, patients on dapagliflozin showed a significant median increase of klotho [Δ+29.5, (12.9–37.2); p = 0.009] and a non-significant decrease of FGF-23 [Δ−4.6, (−1.7 to −5.4); p = 0.051]. A significant increase in log-klotho (p = 0.011) and a decrease in log-FGF-23 (p = 0.040) were found in the inferential analysis. In conclusion, in patients with stable HFrEF, dapagliflozin led to a short-term increase in klotho and a decrease in FGF-23.
format Online
Article
Text
id pubmed-10515719
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-105157192023-09-23 Short-term changes in klotho and FGF23 in heart failure with reduced ejection fraction—a substudy of the DAPA-VO(2) study Mora-Fernández, Carmen Pérez, Adora Mollar, Anna Palau, Patricia Amiguet, Martina de la Espriella, Rafael Sanchis, Juan Górriz, Jose Luis Soler, María José Navarro-González, Juan F. Núñez, Julio Front Cardiovasc Med Cardiovascular Medicine The klotho and fibroblast growth factor 23 (FGF-23) pathway is implicated in cardiovascular pathophysiology. This substudy aimed to assess the changes in klotho and FGF-23 levels 1-month after dapagliflozin in patients with stable heart failure and reduced ejection fraction (HFrEF). The study included 29 patients (32.2% of the total), with 14 assigned to the placebo group and 15 to the dapagliflozin, as part of the double-blind, randomized clinical trial [DAPA-VO(2) (NCT04197635)]. Blood samples were collected at baseline and after 30 days, and Klotho and FGF-23 levels were measured using ELISA Kits. Between-treatment changes (raw data) were analyzed by using the Mann-Whitney test and expressed as median (p25%–p75%). Linear regression models were utilized to analyze changes in the logarithm (log) of klotho and FGF-23. The median age was 68.3 years (60.8–72.1), with 79.3% male and 81.5% classified as NYHA II. The baseline medians of left ventricular ejection fraction, glomerular filtration rate, NT-proBNP, klotho, and FGF-23 were 35.8% (30.5–37.8), 67.4 ml/min/1.73 m(2) (50.7–82.8), 1,285 pg/ml (898–2,305), 623.4 pg/ml (533.5–736.6), and 72.6 RU/ml (62.6–96.1), respectively. The baseline mean peak oxygen uptake was 13.1 ± 4.0 ml/kg/min. Compared to placebo, patients on dapagliflozin showed a significant median increase of klotho [Δ+29.5, (12.9–37.2); p = 0.009] and a non-significant decrease of FGF-23 [Δ−4.6, (−1.7 to −5.4); p = 0.051]. A significant increase in log-klotho (p = 0.011) and a decrease in log-FGF-23 (p = 0.040) were found in the inferential analysis. In conclusion, in patients with stable HFrEF, dapagliflozin led to a short-term increase in klotho and a decrease in FGF-23. Frontiers Media S.A. 2023-08-25 /pmc/articles/PMC10515719/ /pubmed/37745119 http://dx.doi.org/10.3389/fcvm.2023.1242108 Text en © 2023 Mora-Fernández, Pérez, Mollar, Palau, Amiguet, de la Espriella, Sanchis, Górriz, Soler, Navarro-González, Núñez and DAPA-VO2 Investigators. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Mora-Fernández, Carmen
Pérez, Adora
Mollar, Anna
Palau, Patricia
Amiguet, Martina
de la Espriella, Rafael
Sanchis, Juan
Górriz, Jose Luis
Soler, María José
Navarro-González, Juan F.
Núñez, Julio
Short-term changes in klotho and FGF23 in heart failure with reduced ejection fraction—a substudy of the DAPA-VO(2) study
title Short-term changes in klotho and FGF23 in heart failure with reduced ejection fraction—a substudy of the DAPA-VO(2) study
title_full Short-term changes in klotho and FGF23 in heart failure with reduced ejection fraction—a substudy of the DAPA-VO(2) study
title_fullStr Short-term changes in klotho and FGF23 in heart failure with reduced ejection fraction—a substudy of the DAPA-VO(2) study
title_full_unstemmed Short-term changes in klotho and FGF23 in heart failure with reduced ejection fraction—a substudy of the DAPA-VO(2) study
title_short Short-term changes in klotho and FGF23 in heart failure with reduced ejection fraction—a substudy of the DAPA-VO(2) study
title_sort short-term changes in klotho and fgf23 in heart failure with reduced ejection fraction—a substudy of the dapa-vo(2) study
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10515719/
https://www.ncbi.nlm.nih.gov/pubmed/37745119
http://dx.doi.org/10.3389/fcvm.2023.1242108
work_keys_str_mv AT morafernandezcarmen shorttermchangesinklothoandfgf23inheartfailurewithreducedejectionfractionasubstudyofthedapavo2study
AT perezadora shorttermchangesinklothoandfgf23inheartfailurewithreducedejectionfractionasubstudyofthedapavo2study
AT mollaranna shorttermchangesinklothoandfgf23inheartfailurewithreducedejectionfractionasubstudyofthedapavo2study
AT palaupatricia shorttermchangesinklothoandfgf23inheartfailurewithreducedejectionfractionasubstudyofthedapavo2study
AT amiguetmartina shorttermchangesinklothoandfgf23inheartfailurewithreducedejectionfractionasubstudyofthedapavo2study
AT delaespriellarafael shorttermchangesinklothoandfgf23inheartfailurewithreducedejectionfractionasubstudyofthedapavo2study
AT sanchisjuan shorttermchangesinklothoandfgf23inheartfailurewithreducedejectionfractionasubstudyofthedapavo2study
AT gorrizjoseluis shorttermchangesinklothoandfgf23inheartfailurewithreducedejectionfractionasubstudyofthedapavo2study
AT solermariajose shorttermchangesinklothoandfgf23inheartfailurewithreducedejectionfractionasubstudyofthedapavo2study
AT navarrogonzalezjuanf shorttermchangesinklothoandfgf23inheartfailurewithreducedejectionfractionasubstudyofthedapavo2study
AT nunezjulio shorttermchangesinklothoandfgf23inheartfailurewithreducedejectionfractionasubstudyofthedapavo2study
AT shorttermchangesinklothoandfgf23inheartfailurewithreducedejectionfractionasubstudyofthedapavo2study