Growth differentiation factor-15 and N-terminal pro-BNP in acute heart failure with preserved ejection fraction.

Aims: Heart failure with preserved ejection fraction (HFpEF) continues to be an increasingly common health problem associated with a high mortality rate. Elevated levels of Growth differentiation factor-15 (GDF15) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are reportedly associated with poor clinical outcomes in a broad range of cardiovascular diseases. The aim of the present study was to examine the effect of the combined assessment of these markers on clinical outcomes in patients with HFpEF.

Methods: This study is the prospective observational study. We measured the serum levels of GDF15 and NT-proBNP in 643 patients (mean age 73 ± 12, 42% females). All patients were prospectively followed up for a median period of 1998 days. Total 132 HF-related events and 88 all-cause deaths occurred during the follow-up period.

Results: Multivariate Cox proportional hazards regression analysis demonstrated that both serum GDF15 and NT-proBNP levels were independently associated with HF-related events after adjustment for confounding risk factors (GDF15: hazard ratio, 1.72; 95% confidence interval, 1.35-2.19; P < 0.0001 and NT-proBNP: hazard ratio, 1.63; 95% confidence interval, 1.25-2.13; P = 0.0003). Serum GDF15 levels improved the prediction capacity for HF-related events (0.7405 vs. 0.7190; P = 0.0422), with a significant net reclassification index (0.2724) and integrated discrimination improvement (0.0246). The C indices of GDF15 for HF-related events and all-cause deaths were significantly larger than those of NT-proBNP in men (HF-related events: 0.7389 vs. 0.6721; P = 0.0393, and all-cause deaths: 0.6922 vs.0.6109; P = 0.0262) but not in women. The combination of GDF15 and NT-proBNP levels stratified patients with HFpEF, identifying those at a high risk for HF-related events and all-cause deaths.

Conclusions: Serum GDF15 could be an additional prognostic information to NT-proBNP in patients with HFpEF. The prognostic abilities of serum GDF15 and NT-proBNP differed according to sex. These markers were the feasible markers for patients with HFpEF, identifying those at a high risk for HF-related events and all-cause deaths.