​Meta-analysis of the applied value of the growth differentiation factor 15 detection in HFpEF diagnosis

To systematically evaluate the diagnostic value of growth differentiation factor-15 (GDF-15) for heart failure with preserved ejection fraction (HFpEF).

Chinese and English literature on the diagnosis of HFpEF using GDF-15 were searched in PubMed, Embase, Web of Science (WOS), Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, WanFang Database, and others. The literature on the diagnostic value of the GDF-15 test for HFpEF was screened from the establishment of the database to April 2023 according to the inclusion and exclusion criteria. The quality of the included studies was then assessed based on the QUADAS-2 list, and the threshold effect was evaluated using the Meta-Disc1.4 software. STATA 17.0 software was used to combine the sensitivity, specificity, and area under the curve (AUC) of the included studies. Moreover, heterogeneity was evaluated by the inconsistency index (I²) and Cochrane Q index, and the source of heterogeneity was explored by subgroup analysis, meta-regression, and sensitivity analysis. Finally, Deek's quantitative funnel plot was used to assess whether there was publication bias among the included studies.

A total of ten studies involving 1550 patients were included. The pooled sensitivity was 0.77 (95%CI: 0.70-0.83), the specificity was 0.79 (95%CI: 0.68-0.87), the positive likelihood ratio was 3.9 (95%CI: 2.6-5.9), and the negative likelihood ratio was 0.21 (95%CI:0.12-0.36). The diagnostic odds ratio was 19 (95%CI: 9-37), and the AUC of SROC was 0.88 (95%CI: 0.85-0.9). The results of the heterogeneity test showed significant heterogeneity among the studies (I² = 96%, p = 0.000 < 0.01). Meta-regression analysis showed that there was a significant difference in diagnostic efficacy between the gold standard group (p = 0.0064 < 0.05), while there was no significant difference in diagnostic efficacy among the three subgroups of age, gender, and comprehensive group (p > 0.05). After excluding the articles that did not include biomarkers for the diagnosis of HFpEF, the average age ≥73 years old, and the proportion of women >55%, the remaining four articles had the pooled sensitivity of 0.80 (I² = 60.1%, p = 0.06 >​ 0.05) and the pooled specificity of 0.84 (I² = 0%, p = 0.61 >​0.05), which insisted that there is no significant heterogeneity among them.

With its high sensitivity and specificity for HFpEF diagnosis, GDF-15 is a novel biomarker for HFpEF diagnosis.