Fibroblast Growth Factor 23 and Exercise Capacity in Heart Failure with Preserved Ejection Fraction

J Card Fail. 2021 Mar;27(3):309-317. doi: 10.1016/j.cardfail.2020.09.477. Epub 2020 Oct 7.

Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) is characterized by left ventricular hypertrophy and decreased exercise capacity. Fibroblast growth factor 23 (FGF23), a hormone involved in phosphate, vitamin D, and iron homeostasis, is linked to left ventricular hypertrophy and HF. We measured c-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels and examined their associations with exercise capacity in patients with HFpEF.

Methods and results: Using multivariable linear regression and linear mixed models, we studied the associations of cFGF23 and iFGF23 with baseline and mean weekly change over 24 weeks in peak oxygen consumption and 6-minute walk distance in individuals enrolled in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF trial. Our study population included 172 individuals with available plasma for cFGF23 and iFGF23 measurements. Median (25th-75th percentile) baseline cFGF23 and iFGF23 levels were 208.7 RU/mL (132.1-379.5 RU/mL) and 90.3 pg/mL (68.6-128.5 pg/mL), respectively. After adjustment for cardiovascular disease and hematologic and kidney parameters, higher cFGF23 was independently associated with a lower peak oxygen consumption at baseline. Higher iFGF23 was independently associated with shorter 6-minute walk distance at baseline. No significant associations were appreciated with the longitudinal outcomes.

Conclusions: In patients with HFpEF, higher FGF23 levels are independently associated with decreased exercise capacity at baseline.

Keywords: Heart failure with preserved ejection fraction; chronic kidney disease; exercise capacity; fibroblast growth factor 23.

MeSH terms

  • Exercise Tolerance
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors
  • Heart Failure*
  • Humans
  • Stroke Volume

Substances

  • FGF23 protein, human
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23