Diagnostic and prognostic implications of growth differentiation factor 15 in heart failure with preserved ejection fraction: a systematic review and meta-analysis
Bibliographic record
Abstract
Background 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. Methods 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). Results 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. Conclusion 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.018 | 0.043 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.018 | 0.034 |
| Bibliometrics | 0.008 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".