Fibroblast Growth Factor-23 and Death, Heart Failure, and Cardiovascular Events in Community-Living Individuals: CHS (Cardiovascular Health Study)

Study Questions:

Are plasma levels of fibroblast growth factor (FGF)-23 associated with cardiovascular disease (CVD)?

Methods:

Plasma FGF-23 was measured in 3,107 community-living persons ≥65 years of age, and participants were followed for 10.5 years for development of heart failure (HF) and CVD events. Associations of FGF-23 with each outcome were evaluated using Cox proportional hazards models. Effects of chronic kidney disease (CKD) status on associations were also tested.

Results:

Lower glomerular filtration rate and higher urine albumin-to-creatinine ratios were associated with high FGF-23 at baseline. During follow-up, there were 1,730 deaths, 697 HF events, and 797 CVD events. Although high FGF-23 concentrations were associated with each outcome in combined analyses, the associations were stronger for those with CKD (p interactions all ≤0.006). In the CKD group (n = 1,128), the highest FGF-23 quartile had adjusted hazards ratios (HRs) of 1.87 for all-cause death, 1.94 for HF, and 1.49 for CVD events compared with the lowest quartile. Corresponding HRs in those without CKD (n = 1,979) were 1.29, 1.37, and 1.07.

Conclusions:

The authors concluded that FGF-23 is independently associated with all-cause mortality and incident HF in community-living older persons. These associations appear stronger in persons with CKD.

Perspective:

Plasma levels of FGF-23 rise with renal failure, possibly as a mechanism to maintain normal serum phosphate levels. Other studies have shown that higher levels of FGF-23 in patients with kidney disease or documented CVD are associated with increased mortality. This study extends these previous findings by demonstrating that this association persists in community-living older adults, although the association appears much stronger in the setting of CKD. FGF-23 may be a link between CKD and adverse outcomes, and these findings raise the possibility that therapeutic targeting of FGF-23 may be beneficial, especially in patients with kidney disease.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Cause of Death, Proportional Hazards Models, Kidney Diseases, Biological Markers, Heart Failure, Cardiovascular Diseases, Fibroblast Growth Factors


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