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Am J Kidney Dis. 2015 Jul;66(1):40-6. doi: 10.1053/j.ajkd.2014.10.025. Epub 2015 Jan 5.

Fibroblast growth factor 23 and sudden versus non-sudden cardiac death: the Cardiovascular Health Study.

Author information

1
Section of Electrophysiology, Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia, PA. Electronic address: rajat.deo@uphs.upenn.edu.
2
Kidney Research Institute, University of Washington, Seattle, WA.
3
Kidney Research Institute, University of Washington, Seattle, WA; Division of Nephrology, University of Washington, Seattle, WA.
4
Division of Cardiology, University of Washington, Seattle, WA.
5
Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA.
6
Division of Renal Diseases and Hypertension, University of Colorado Denver Health Sciences Center, Aurora, CO.
7
Division of Nephrology, Tufts Medical Center, Boston, MA.
8
Cardiovascular Health Research Unit, University of Washington, Seattle, WA; Department of Medicine, University of Washington, Seattle, WA; Department of Epidemiology, University of Washington, Seattle, WA; Department of Health Services, University of Washington, Seattle, WA; Center for Health Studies, Group Health, Seattle, WA.
9
General Internal Medicine Section, Veterans Affairs Medical Center, San Francisco, CA; Department of Medicine, University of California, San Francisco, CA; Department of Epidemiology, University of California, San Francisco, CA; Department of Biostatistics, University of California, San Francisco, CA.
10
Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, San Diego, CA; Division of Nephrology and Preventive Medicine, University of California, San Diego, San Diego, CA.

Abstract

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.

KEYWORDS:

Cardiovascular Health Study (CHS); Fibroblast growth factor 23 (FGF-23); cardiovascular event; cardiovascular mortality; chronic kidney disease (CKD); cohort study; fatal arrhythmic event; non-SCD; renal function; sudden cardiac death (SCD)

PMID:
25572028
PMCID:
PMC4485528
DOI:
10.1053/j.ajkd.2014.10.025
[Indexed for MEDLINE]
Free PMC Article

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