Abstract P241: Fibroblast Growth Factor-23 and Death, Heart Failure, and Cardiovascular Events in Community-Living Individuals: the Cardiovascular Health Study
Authors: Ix Joachim H , Katz Ronit , Kestenbaum Bryan , de Boer Ian , Chonchol Michel , Mukamal Kenneth , Rifkin Dena , Siscovick David , Sarnak Mark , Shlipak Michael 
Published: July 2021

Background:
Fibroblast growth factor-23 (FGF23) increases renal phosphorus excretion and inhibits calcitriol synthesis. In advanced chronic kidney disease (CKD), high FGF23 levels are associated with increased mortality. The relationship of FGF23 with all-cause mortality, incident heart failure (HF), and incident cardiovascular disease (CVD) in community-living populations is uncertain

Methods:
Among 3,107 community-living individuals aged > 65 years, we measured plasma FGF23 concentrations in 1996-97. Follow-up for death and adjudicated HF and CVD events continued through 2008. Cox proportional hazards models evaluated associations of FGF23 with each outcome. We tested interactions by CKD status (eGFR < 60ml/min/1.73m
2
or ACR ≥ 30mg/g).

Results:
During 10.5 years median follow-up, there were 1,730 deaths, 697 adjudicated incident HF events, and 797 adjudicated incident CVD events. FGF23 was elevated in persons with eGFR < 80ml/min/1.73m
2
or with urine ACR > 30mg/g. Although higher FGF23 concentrations were associated with death and HF o in combined analyses when adjusted for traditional CVD risk factors and kidney function (HR 1.25 [1.14, 1.36] for death, 1.41 [1.23, 1.61] for HF, and 1.12 [0.98, 1.29] for CVD), the associations were consistently stronger for those with CKD (all P interactions < 0.006;
Table
).

Conclusions:
FGF23, a hormone involved in phosphorous and vitamin D homeostasis, is independently associated with all-cause death and incident HF in community-living older persons. These relationships appear stronger in persons with CKD.

Association of FGF23 with Incident Heart Failure, Cardiovascular Disease, and All-Cause Death Stratified by CKD. The Cardiovascular Health Study

FGF23 Quartiles
Linear model

1
2
3
4
Per Doubling of FGF23
P-value

FGF23 Range (RU/mL)
< 51
51-70
71-100
> 100

Chronic Kidney Disease
(N=1,128)

    All-Cause Mortality

        Annual event rate (# events / # at risk)
7.7 (90/141)
7.6 (150/235)
8.7 (191/285)
14.3 (404/467)

        Adjusted
*
HR (95% CI)

1.00 (ref)
0.97 (0.75, 1.26)
1.09 (0.84, 1.41)
1.87 (1.47, 2.38)
1.41 (1.30, 1.52)
<0.001

    Incident Heart Failure
†

        Annual event rate (# events / # at risk)
3.7 (38/136)
3.8 (63/213)
4.6 (81/256)
7.7 (145/350)

        Adjusted
*
HR (95% CI)

1.00 (ref)
0.97 (0.64, 1.46)
1.16 (0.78, 1.73)
1.94 (1.32, 2.83)
1.52 (1.33, 1.72)
<0.001

    Incident Cardiovascular Disease
‡

        Annual event rate (# events / # at risk)
5.1 (39/104)
6.2 (71/156)
6.2 (76/184)
9.5 (126/257)

        Adjusted
*
HR (95% CI)

1.00 (ref)
1.09 (0.74, 1.63)
1.09 (0.73, 1.62)
1.49 (1.02, 2.18)
1.24 (1.09, 1.43)
0.002

No Chronic Kidney Disease
(N=1,979)

    All-Cause Mortality

        Annual event rate (# events / # at risk)
4.3 (270/651)
4.8 (247/550)
5.0 (228/489)
5.9 (150/289)

        Adjusted
*
HR (95% CI)

1.00 (ref)
1.10 (0.93, 1.32)
1.15 (0.96, 1.38)
1.29 (1.05, 1.59)
1.07 (0.98, 1.17)
0.15

    Incident Heart Failure
†

        Annual event rate (# events / # at risk)
1.9 (109/631)
2.3 (106/531)
2.3 (91/463)
3.1 (64/256)

        Adjusted
*
HR (95% CI)

1.00 (ref)
1.19 (0.90, 1.56)
1.11 (0.84, 1.48)
1.37 (0.99, 1.89)
1.17 (1.02, 1.33)
0.023

    Incident Cardiovascular Disease
‡

        Annual event rate (# events / # at risk)
3.5 (149/496)
4.0 (142/431)
4.2 (129/374)
4.0 (65/204)

        Adjusted
*
HR (95% CI)

1.00 (ref)
1.12 (0.89, 1.42)
1.16 (0.91, 1.42)
1.07 (0.79, 1.45)
0.99 (0.87, 1.13)
0.899

P-values for interaction in the adjusted model were < 0.001 for all cause mortality, 0.008 for incident HF, and 0.006 for incident CVD

†

Excludes 271 participants with prevalent HF at baseline.

‡

Excludes 901 participants with prevalent CVD at baseline

*

Adjusted for age, sex, race, health status (fair or poor vs. better), current smoking, prior stroke, prior MI, prior HF, prior claudication, hypertension, diabetes (nl, ifg, dm), bmi, estrogen use (women), total chol, lipid med use, natural log (CRP).

Funding(This research has received full or partial funding support from the American Heart Association, National Center)