Short-term changes in klotho and FGF23 in heart failure with reduced ejection fraction-a substudy of the DAPA-VO₂ study

Autores de INCLIVA

• Adoración Pérez Sanchez

  Autor

• Anna Mireia Mollar Fernandez

  Autor

• Patricia Palau Sampio

  Autor

• 

  Rafael De La Espriella Juan

  Autor

• 

  Juan Sanchis Fores

  Autor

• 

  Jose Luis Górriz Teruel

  Autor

• 

  Julio Nuñez Villota

  Autor

Participantes ajenos a INCLIVA

• Mora-Fernández, C
• Amiguet, M
• Soler, MJ
• Navarro-González, JF
• DAPA-VO2 Investigators

Grupos y Plataformas de I+D+i

• Grupo de Enfermedad Renal

  

  Leading Researcher

  Jose Luis Górriz Teruel

• Grupo de investigación en Cardiología Clínica

  

  Leading Researcher

  Juan Sanchis Fores

• Grupo de Investigación en Insuficiencia Cardiaca

  

  Established Researcher

  Julio Nuñez Villota

Abstract

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-VO2 (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 [Delta+29.5, (12.9-37.2); p = 0.009] and a non-significant decrease of FGF-23 [Delta-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.

© 2023 Mora-Fernández, Pérez, Mollar, Palau, Amiguet, de la Espriella, Sanchis, Górriz, Soler, Navarro-González, Núñez and DAPA-VO2 Investigators.

Keywords

• dapagliflozin; fibroblast growth factor 23; functional capacity; heart failure with reduced ejection fraction; klotho; peak oxygen consumption