Fibroblast Growth Factor-23 and Risks of Cardiovascular and Noncardiovascular Diseases: A Meta-Analysis

Area of Science:

• Nephrology
• Cardiology
• Endocrinology

Background:

• Fibroblast growth factor-23 (FGF-23) is implicated in the elevated cardiovascular disease (CVD) risk observed in chronic kidney disease (CKD) patients.
• Understanding the precise role of FGF-23 in CVD pathogenesis is crucial for risk stratification and therapeutic strategies in CKD.

Purpose of the Study:

• To investigate the association between FGF-23 concentrations and the risk of cardiovascular events in prospective studies.
• To determine if the relationship between FGF-23 and cardiovascular risk is dose-dependent and potentially causal.

Main Methods:

• A systematic review and meta-analysis of prospective studies examining FGF-23 levels and cardiovascular event risk.
• Risk ratios (RRs) were extracted and standardized to compare top versus bottom thirds of baseline FGF-23 concentrations.
• Analysis included cohorts from the general population, CKD patients not on dialysis, and patients on dialysis.

Main Results:

• Elevated FGF-23 concentrations were associated with increased risks of myocardial infarction (RR 1.33), stroke (RR 1.26), heart failure (RR 1.48), and cardiovascular mortality (RR 1.42).
• Similarly, higher FGF-23 levels correlated with increased all-cause mortality (RR 1.70) and noncardiovascular mortality (RR 1.52).
• No clear exposure-response trend was observed across studies, irrespective of FGF-23 concentration differences.

Conclusions:

• The similar magnitude of association between high FGF-23 levels and both cardiovascular and noncardiovascular outcomes suggests a potential non-causal relationship.
• The absence of a dose-response relationship further supports the hypothesis that FGF-23 may be a marker rather than a direct cause of cardiovascular risk in CKD.