FGF-23, Left Ventricular Hypertrophy, and Mortality in Patients With CKD: A Revisit With Mediation Analysis.
JACC Adv
; 3(1): 100747, 2024 Jan.
Article
in En
| MEDLINE
| ID: mdl-38939808
ABSTRACT
Background:
In patients with chronic kidney disease (CKD), fibroblast growth factor (FGF)-23 is suspected to cause death or cardiovascular disease by inducing left ventricular hypertrophy (LVH).Objectives:
This study aims to quantify the mediational effect of LVH in the hypothetical causal pathway from FGF-23 to long-term adverse outcomes.Methods:
From 3,939 adults with CKD stages 2 to 4 enrolled in the CRIC (Chronic Renal Insufficiency Cohort) study, 2,368 participants with available data of FGF-23, left ventricular mass index at 1 year, and covariates were included. We employed linear and Cox proportional hazards regression models to investigate the association between FGF-23 and LVH, all-cause mortality, atrial fibrillation (AF), or congestive heart failure (CHF). Mediation analysis was used within a counterfactual framework to decompose the effect of FGF-23 into natural direct and indirect effects.Results:
Among 2,368 participants (mean age 57.7 years, 1,252 males, median FGF-23 level 138.8 RU/mL), left ventricular mass index was positively correlated with FGF-23. During a median of 12.0, 11.1, and 11.1 years, FGF-23 was associated with all-cause mortality (HR 1.62, 95% CI 1.24-2.12), AF (HR 1.58, 95% CI 1.12-2.24), and CHF (HR 1.32, 95% CI 0.95-1.84) when the highest quartile was compared to the lowest quartile. LVH mediated 7.4%, 11.2%, and 21.9% of the effect of FGF-23 on all-cause mortality, AF, and CHF, respectively.Conclusions:
In CKD patients, FGF-23 had a minor effect on the development of long-term adverse outcomes through LVH. Other potential mediators and the validity of negative effect of FGF-23 should be explored.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
JACC Adv
Year:
2024
Document type:
Article
Affiliation country:
Japan