Data_Sheet_1_Relationship between serum growth differentiation factor 15, fibroblast growth factor-23 and risk of atrial fibrillation: A systematic review and meta-analysis.docx

Background and objectiveGrowth differentiation factor-15 (GDF-15) and fibroblast growth factor-23 (FGF-23) are considered predictors of the incidence of cardiovascular diseases. The present meta-analysis aimed to elucidate the associations between GDF-15 and FGF-23 in the risk of atrial fibrillation (AF).
MethodsAn electronic search was conducted in the Cochrane Library, PubMed, and Embase databases from inception until February 27, 2021. The study protocol was registered in the PROSPERO database (CRD42020182226).
ResultsIn total, 15 studies that enrolled 36,017 participants were included. Both serum FGF-23 and GDF-15 were elevated in patients with AF. Analysis of categorical variables showed higher serum FGF-23 levels were associated with an increased risk of AF [relative risk (RR) = 1.28, 95% confidence interval (CI): 1.05–1.56]. In contrast, this association was not found with GDF-15 (RR = 0.91, 95% CI: 0.20–4.04). In dose-response analysis, a linear positive association was noted between serum FGF-23 levels and the risk of AF (P nonlinear = 0.9507), with a RR elevation of 7% for every 20 pg/ml increase in the serum FGF-23 levels (95% CI: 1.02–1.13). No remarkable relationship was found between serum GDF-15 levels and the risk of AF, and the overall RR for the association between a 100 ng/L increment in GDF-15 levels and AF was 1.01 (95% CI: 0.998–1.02).
ConclusionOur study showed a positive linear correlation between serum FGF-23 levels and the risk of AF. However, no significant association was found between GDF-15 and the risk of AF. Further studies are warranted to clarify whether serum FGF-23 levels may be considered in predicting the risk of AF.
Systematic Review Registration:http:www.york.ac.uk/inst/crd, identifier CRD42020182226.

背景与目的：生长分化因子-15（growth differentiation factor-15, GDF-15）与成纤维细胞生长因子-23（fibroblast growth factor-23, FGF-23）被认为是心血管疾病发病的预测标志物。本项荟萃分析旨在阐明GDF-15、FGF-23与心房颤动（atrial fibrillation, AF）发病风险之间的关联。
方法：本研究于2021年2月27日前，在Cochrane图书馆、PubMed及Embase数据库中开展电子文献检索。研究方案已在PROSPERO数据库注册（注册号：CRD42020182226）。
结果：最终共纳入15项研究，合计纳入36017名受试者。心房颤动患者的血清FGF-23与GDF-15水平均升高。分类变量分析显示，血清FGF-23水平升高与心房颤动风险增加相关[相对危险度（relative risk, RR）=1.28，95%置信区间（confidence interval, CI）：1.05~1.56]。与之相反，未观察到GDF-15与心房颤动风险存在此类关联（RR=0.91，95%CI：0.20~4.04）。剂量反应分析显示，血清FGF-23水平与心房颤动风险呈线性正相关（非线性检验P=0.9507），血清FGF-23每升高20pg/ml，心房颤动风险升高7%（95%CI：1.02~1.13）。未发现血清GDF-15水平与心房颤动风险存在显著关联，GDF-15每升高100ng/L时，其与心房颤动关联的合并RR值为1.01（95%CI：0.998~1.02）。
结论：本研究结果显示，血清FGF-23水平与心房颤动风险呈线性正相关。但未发现GDF-15与心房颤动风险存在显著关联。未来仍需开展进一步研究，以明确血清FGF-23水平是否可用于心房颤动风险的预测。
系统评价注册：http://www.york.ac.uk/inst/crd，注册号：CRD42020182226。