Fibroblast Growth Factor 23 and Exercise Capacity in Heart Failure with Preserved Ejection Fraction: FGF23 and Exercise Capacity in HFpEF

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.