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. 2021 Aug 26:8:705273.
doi: 10.3389/fcvm.2021.705273. eCollection 2021.

High-Level Serum Fibroblast Growth Factor 21 Concentration Is Closely Associated With an Increased Risk of Cardiovascular Diseases: A Systematic Review and Meta-Analysis

Yucong Zhang  1 , Jinhua Yan  1 , Ni Yang  1 , Zonghao Qian  1 , Hao Nie  1 , Zhen Yang  1 , Dan Yan  1 , Xiuxian Wei  1 , Lei Ruan  1 , Yi Huang  1 , Cuntai Zhang  1 , Le Zhang  1
Affiliations

High-Level Serum Fibroblast Growth Factor 21 Concentration Is Closely Associated With an Increased Risk of Cardiovascular Diseases: A Systematic Review and Meta-Analysis

Yucong Zhang et al. Front Cardiovasc Med. .

Abstract

Background: The association between fibroblast growth factor 21 (FGF21) and cardiovascular disease (CVD) risk remains unclear. We conducted this systematic review and meta-analysis to evaluate the association between FGF21 and CVDs, and relevant vascular parameters. Methods: PubMed and Web of Science databases were systematically searched to identify relevant studies published before March 2021. The FGF21 concentration was compared between individuals with and without CVDs. The effect of FGF21 on CVD risk was assessed by using hazard ratio (HR) and odds ratio (OR). The association between FGF21 and vascular parameters was assessed by Pearson's r. Study quality was assessed using Newcastle-Ottawa Scale and Joanna Briggs Institution Checklist. Results: A total of 29,156 individuals from 30 studies were included. Overall, the serum FGF21 concentration was significantly higher in CVD patients (p < 0.001), especially for coronary artery disease (CAD) (p < 0.001) and hypertension (p < 0.001). The pooled OR (p = 0.009) and HR (p < 0.001) showed that the risk of CVDs increased with FGF21. The linear association between FGF21 and vascular parameters, including pulse wave velocity (r = 0.32), carotid intima-media thickness (r = 0.21), ankle-brachial index (r = 0.33), systolic blood pressure (r = 0.13), and diastolic blood pressure (r = 0.05), was insignificant. The incidence of overall CVDs (p = 0.03) was significantly higher in individuals with higher FGF21 levels. Conclusion: High-level serum FGF21 concentration is closely associated with an increased risk of CVDs, which may be independent of vascular parameters. A standard FGF21 classification threshold needs to be established before clinical use for CVD risk assessment. Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=241968, identifier: CRD42021241968.

Keywords: cardiovascular disease; coronary heart disease; fibroblast growth factor 21; hypertension; meta-analysis; risk factor.

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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
Preferred reporting items for systemic reviews and meta-analysis flow diagram of literature screening.
Figure 2
Figure 2
Forest plot of serum FGF21 concentration in individuals with or without CVDs. FGF21, fibroblast growth factor 21; CVD, cardiovascular disease. Mean value refers to the mean serum FGF21 concentration in each group.
Figure 3
Figure 3
Forest plot of serum FGF21 concentration on the risk of CVDs. (A) Odds ratio; (B) Hazard ratio. FGF21, fibroblast growth factor 21; CVD, cardiovascular disease.
Figure 4
Figure 4
Forest plot of linear association between FGF21 and vascular parameters. (A) Systolic blood pressure; (B) diastolic blood pressure; (C) pulse wave velocity; (D) carotid intima-media thickness; (E) ankle-brachial index. FGF21, fibroblast growth factor 21. Linear association between FGF21 and vascular parameters was assessed by Pearson's r. Pearson's r was transformed into Fisher's Z-value for pooled estimates.
Figure 5
Figure 5
Forest plot of incidence of cardiovascular disease in individuals with different FGF21 levels. FGF21, fibroblast growth factor 21. Events refer to the numbers of corresponding disease that were diagnosed in each group.
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