Diagnostic and prognostic implications of growth differentiation factor 15 in heart failure with preserved ejection...

Growth differentiation factor-15 (GDF-15), an emerging biomarker associated with chronic inflammation and oxidative stress, shows potential diagnostic and prognostic significance for heart failure with preserved ejection fraction (HFpEF). This study aimed to assess the diagnostic and prognostic value of GDF-15 in HFpEF.

Three databases (PubMed, Scopus, and ScienceDirect) were used to search for relevant literature published before August 6, 2024. Quality assessment was conducted using the Newcastle-Ottawa scale and its adaptation for cross-sectional studies. Statistical analysis was performed using RStudio version 4.4.1. All meta-analyses employed a random-effects model. Sensitivity analysis was conducted using the leave-one-out technique to evaluate the influence of individual studies on pooled estimates. This study protocol was registered in PROSPERO (CRD42024569609).

A total of 5,696 HFpEF patients were identified from 28,193 individuals across 12 observational studies. GDF-15 levels were consistently elevated in HFpEF patients, with a pooled mean difference (MD) of 647.60 pg/mL (95% CI [148.43-1,146.77]; p = 0.01). Sensitivity analysis confirmed the robustness of this finding, with a slightly higher MD observed when studies involving HFpEF patients with atrial fibrillation were excluded. Qualitative analysis suggested that the overall diagnostic performance of GDF-15 in HFpEF is slightly superior to conventional biomarkers. GDF-15 showed a pooled area under the curve (AUC) of 0.82 (95% CI [0.72-0.91]), indicating good diagnostic accuracy. Additionally, GDF-15 was associated with increased risk of all-cause mortality and heart failure hospitalisation, with pooled hazard ratios (HR) of 1.46 (95% CI [1.30-1.62]; p < 0.01) and 1.76 (95% CI [1.30-2.38]; p < 0.01), respectively.

GDF-15 demonstrates significant diagnostic and prognostic potential for HFpEF. Elevated GDF-15 levels are associated with increased risk of all-cause mortality and heart failure hospitalisation.