Fibroblast Growth Factor-23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

Abstract

Background Higher fibroblast growth factor-23 ( FGF -23) levels are associated with incident heart failure ( HF ) in MESA (the Multiethnic Study of Atherosclerosis). FGF -23 is also associated with left ventricular hypertrophy. Whether the FGF -23 association with HF is similar for heart failure with reduced ejection fraction ( HF r EF ) and heart failure with preserved ejection fraction ( HF p EF ) is not well established. Methods and Results We studied 6542 participants (mean age 62±10 years, 53% women, mean estimated glomerular filtration rate of 81±18 mL/min per 73 m²) from MESA who were free of cardiovascular disease at baseline (2000-2002). HF events were ascertained by an adjudication committee for a median follow-up of 12.1 years. We classified HF events as HF r EF (ejection fraction [ EF ] <50%) or HF p EF [ EF ] ≥50%) at the time of diagnosis. Cox proportional hazard regression was used to compute hazard ratios and 95% confidence intervals for the association between baseline serum FGF -23 and incident HF r EF and HF p EF . A total of 134 events were classified as HF p EF , 151 HF r EF , and 49 unknown EF . Following imputation, 149 were classified as HF p EF , 176 HF r EF , and 291 participants had HF (34 participants had HF p EF then HF r EF ). In the fully adjusted model, higher FGF -23 levels were associated with incident HF p EF but not with HF r EF (hazard ratio 1.29, 95% confidence interval, 1.08-1.54) versus (hazard ratio 1.04, 95% confidence interval, 0.84-1.29) for each 20 pg/mL higher serum FGF -23 concentration. Conclusions FGF -23 association with HF is driven by the association with HF p EF but not with HF r EF in a population-based cohort. Further studies are needed to determine the pathological mechanisms mediating this association.

Keywords: ejection fraction; fibroblast growth factor; heart failure; left ventricular hypertrophy.

Figure 1

Participant enrollment for the current study. CKD indicates chronic kidney disease; CMR, cardiac magnetic resonance; EF, ejection fraction; FGF‐23, fibroblast growth factor‐23; HF, heart failure; LVM, left ventricular mass.

Figure 2

Hazard ratios of FGF‐23 for incident HF, HFrEF, and HFpEF using restricted cubic spline Cox model analysis: The Multiethnic Study of Atherosclerosis. CI indicates confidence interval; FGF‐23, fibroblast growth factor‐23; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction.

Figure 3

Incidence rates (per 1000 person‐years) by FGF‐23 quartiles of incident HFrEF and HFpEF: The Multiethnic Study of Atherosclerosis. FGF‐23 indicates fibroblast growth factor‐23; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction.