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. 2022 Nov 3:9:989574.
doi: 10.3389/fcvm.2022.989574. eCollection 2022.

Fibroblast growth factor-23 and the risk of cardiovascular diseases and mortality in the general population: A systematic review and dose-response meta-analysis

Menglu Liu  1 , Panpan Xia  2 , Ziqi Tan  2 , Tiangang Song  2 , Kaibo Mei  3 , Jingfeng Wang  4 , Jianyong Ma  5 , Yuan Jiang  4 , Jing Zhang  6 , Yujie Zhao  1 , Peng Yu  2 , Xiao Liu  4
Affiliations

Fibroblast growth factor-23 and the risk of cardiovascular diseases and mortality in the general population: A systematic review and dose-response meta-analysis

Menglu Liu et al. Front Cardiovasc Med. .

Abstract

Background: In the past decade, fibroblast growth factor 23 (FGF23) has been recognized as an important biomarker of cardiovascular diseases. This study aimed to assess the relationship between FGF23 and the risk of cardiovascular diseases (CVDs) in general populations.

Methods: The protocol was registered prospectively in PROSPERO (CRD42021281837) and two authors independently searched for relevant studies in the PubMed, EMBASE, and Cochrane Library databases. The random effects model was applied.

Results: In total, 29 prospective studies involving 135,576 participants were included. In the general population, the category analysis revealed that elevated FGF23 levels were related to increased risks of myocardial infarction (MI) (RR: 1.40, 95%CI: 1.03-1.89), stroke (RR: 1.20, 95%CI: 1.02-1.43), heart failure (HF) (RR: 1.37, 95%CI: 1.23-1.52), CVD events (RR: 1.22, 95%CI: 0.99-1.51), cardiovascular mortality (RR: 1.46, 95%CI: 1.29-1.65), and all-cause mortality (RR: 1.50, 95%CI: 1.29-1.74). In the continuous analysis, per doubling of FGF23 was associated with increased risks of MI (RR: 1.08, 95%CI: 0.94-1.25), stroke (RR: 1.21, 95%CI: 0.99-1.48), HF (RR: 1.24, 95%CI: 1.14-1.35), CVD events (RR: 1.12, 95%CI: 0.99-1.27), cardiovascular mortality (RR: 1.43, 95%CI: 1.09-1.88), all-cause mortality (RR: 1.37, 95%CI: 1.15-1.62). Furthermore, the dose-response analysis demonstrated a potentially non-linear relationship between FGF23 and stroke, HF, and all-cause mortality. In contrast, a potentially linear relationship between FGF23 and cardiovascular mortality was observed (p for non-linearity = 0.73).

Conclusion: The present study suggests that increased serum FGF23 levels are positively related to CVD events and mortality in the general population. The clinical application of FGF23 levels to predict CVD risk requires further research.

Keywords: FGF23; cardiovascular diseases; heart failure; meta-analysis; mortality; myocardial infarction; stroke.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flowchart of the study selection investigating the association between levels of FGF23 and risk of CVDs in the general population.
FIGURE 2
FIGURE 2
Forest plot for the association between FGF23 level and the risk of MI (A), stroke (C), HF (E), and CVD events (G) in the general population, analyzed as category variable, highest vs. lowest; the association between per doubling of FGF23 increment and the risk of MI (B), stroke (D), HF (F), and CVD events (H) in the general population, analyzed as a continuous variable.
FIGURE 3
FIGURE 3
The dose-response relationship between FGF23 levels and the risk of stroke (A), HF (B), cardiovascular mortality (C), and all-cause mortality (D) in the general population. FGF23 levels were converted to RU/ml and the results were pooled in a one-stage random-effects model. The bold lines indicate the pooled restricted cubic spline model and the black dashed line indicates the 95% CIs of the pooled curve.
FIGURE 4
FIGURE 4
Forest plot for the association between FGF23 levels and the risk of cardiovascular mortality (A) and all-cause mortality (C) in the general population, analyzed as category variable, highest vs. lowest; the association between per doubling of FGF23 increment and the risk of cardiovascular mortality (B), and all-cause mortality (D) in the general population, analyzed as a continuous variable.
See this image and copyright information in PMC

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