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Fibroblast growth factor 23 and sudden versus non-sudden cardiac death: the Cardiovascular Health Study
Rajat Deo1, Ronit Katz2, Ian H de Boer3
1Section of Electrophysiology, Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia, PA.
Insights
Elevated fibroblast growth factor 23 (FGF-23) is linked to non-sudden cardiac death (SCD) risk. FGF-23 levels showed similar associations with SCD and non-SCD in chronic kidney disease patients.
Area of Science:
- Cardiovascular Research
- Nephrology
- Biomarkers
Background:
- Elevated fibroblast growth factor 23 (FGF-23) is linked to cardiovascular events and mortality, particularly in chronic kidney disease (CKD) patients.
- Individuals with CKD face a higher risk of sudden cardiac death (SCD).
Purpose of the Study:
- To investigate whether FGF-23 is a stronger risk factor for SCD compared to non-SCD.
- To determine the association between FGF-23 levels and SCD versus non-SCD in older adults.
Main Methods:
- A cohort study involving 3,244 participants aged 65+ from the Cardiovascular Health Study.
- Plasma FGF-23 concentrations were measured as the predictor.
- Cox proportional hazards models were used to assess associations with SCD and non-SCD, adjusting for various risk factors and kidney function. Stratified analyses were performed for CKD status.
Main Results:
- Higher FGF-23 concentrations were independently associated with non-SCD (HR per doubling, 1.17; 95% CI, 1.06-1.30) after multivariable adjustment.
- FGF-23 was not independently associated with SCD (HR per doubling, 1.07; 95% CI, 0.85-1.35).
- In the CKD subgroup, FGF-23 was independently associated with non-SCD (adjusted HR, 1.26; 95% CI, 1.10-1.45) and showed a similar, though not significant, association with SCD (HR, 1.20; 95% CI, 0.89-1.62).
Conclusions:
- Elevated FGF-23 levels are independently associated with non-SCD in the general population.
- In individuals with CKD, FGF-23 levels demonstrated similar associations with both SCD and non-SCD.
- The study had limited power to detect moderate effects between FGF-23 and SCD.
Background:
Elevated fibroblast growth factor 23 (FGF-23) concentrations are associated with greater risk of cardiovascular events and mortality, especially among people with chronic kidney disease (CKD). Because individuals with CKD are at an increased risk of sudden cardiac death (SCD), we sought to understand whether FGF-23 level is a stronger risk factor for SCD versus non-SCD.
Study Design:
Cohort study.
Setting & Participants:
3,244 participants 65 years or older in the community-based Cardiovascular Health Study.
Predictor:
Plasma FGF-23 concentrations.
Outcomes:
We assessed SCD and non-SCD in these analyses. SCD was adjudicated rigorously and was defined as a sudden pulseless condition of cardiac origin in a previously stable person occurring out of hospital or in the emergency department.
Measurements:
We estimated associations of baseline FGF-23 concentrations with SCD and non-SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, comorbid conditions, and kidney function. We also tested whether associations differed by CKD status.
Results:
During a median follow-up of 8.1 years, there were 118 adjudicated SCD and 570 non-SCD events. After multivariable adjustment for demographics, cardiovascular risk factors, comorbid conditions, and parameters of kidney function, higher FGF-23 concentrations were an independent risk factor for non-SCD (HR [per doubling], 1.17; 95% CI, 1.06-1.30). However, elevated FGF-23 concentrations were not associated independently with SCD (HR [per doubling], 1.07; 95% CI, 0.85-1.35). In stratified analysis by CKD status (36.5% of cohort), doubling of FGF-23 concentrations was associated independently with non-SCD (adjusted HR, 1.26; 95% CI, 1.10-1.45). A similar magnitude of association was observed between FGF-23 level and SCD in the CKD subgroup; however, it was not significant (HR, 1.20; 95% CI, 0.89-1.62).
Limitations:
Limited power to detect moderate-sized effects between FGF-23 level and SCD in both the primary and stratified analyses.
Conclusions:
In this population-based study, FGF-23 level elevations were associated independently with non-SCD. Among individuals with CKD, the associations between FGF-23 level and SCD and non-SCD were similar.
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