FGF23 as a Prognostic Biomarker in Atrial Fibrillation Outcomes
Overview
This study of 35,197 atrial fibrillation (AF) patients from the UK Biobank demonstrates that elevated serum fibroblast growth factor 23 (FGF23) levels are significantly associated with increased risks of all-cause and cardiovascular mortality, as well as heart failure. Genetic analysis using a polygenic score for FGF23 revealed a paradoxical relationship, with increased genetic predisposition linked to reduced heart failure risk but higher all-cause mortality and ischemic stroke risk.
Background
Fibroblast growth factor 23 (FGF23) is a hormone primarily involved in mineral metabolism but has recently been implicated in cardiovascular diseases, including atrial fibrillation (AF). AF is a complex condition influenced by both genetic and environmental factors and is associated with significant morbidity and mortality. While elevated FGF23 levels have been linked to AF prevalence and incidence, its prognostic value in AF patients remains unclear. This study investigates the clinical and genetic associations of FGF23 with AF-related outcomes to assess its potential as a biomarker for prognosis and management.
Data Highlights
Outcome
Association with Serum FGF23 (per SD increase)
Association with PGSFGF23
All-cause mortality
37% increased risk
Increased risk
Cardiovascular mortality
40% increased risk
Not specified
Heart failure (HF)
43% increased risk
Reduced risk
Ischaemic stroke
Not specified
Increased risk
Dementia
Not specified
Not specified
Key Findings
Elevated serum FGF23 levels in AF patients are significantly associated with increased risks of all-cause mortality, cardiovascular mortality, and heart failure.
A polygenic score for FGF23 (PGSFGF23) was developed using seven independent SNPs from genome-wide significant loci.
Genetic predisposition to higher FGF23 levels (PGSFGF23) is paradoxically associated with reduced heart failure risk but increased all-cause mortality and ischemic stroke risk.
The paradox between serum FGF23 levels and genetic FGF23 associations suggests complex underlying mechanisms influencing AF outcomes.
FGF23 may serve as a potential biomarker for risk stratification and prognosis in AF patients.
Clinical Implications
Measurement of serum FGF23 levels could aid clinicians in identifying AF patients at higher risk for mortality and heart failure, potentially guiding more personalized management strategies. However, the contrasting genetic associations highlight the need for cautious interpretation and further research to understand the biological pathways involved before integrating FGF23 testing into routine clinical practice.
Conclusion
FGF23 is a promising biomarker linked to adverse outcomes in atrial fibrillation, with serum levels correlating with increased mortality and heart failure risk. The complex genetic associations underscore the necessity for further studies to clarify the mechanisms and optimize clinical application.
References
Folkersen et al. 2020 -- Genome-wide association study of plasma FGF23 levels
