In multivariable models, the associations of elevated PTH (HR 1.50, 95%CI: 1.13, 1.99) and FGF-23 (HR 1.37, 95%CI: 1.07, 1.75) with incident HF were statistically significant.
In adjusted Cox regression models, higher FGF23 was associated with a 63% greater hazard of incident HF (hazard ratio: 1.63, 95% confidence interval: [1.13-2.36] per 1-unit increase in log-transformed FGF23), which persisted after exclusion of participants with chronic kidney disease (hazard ratio: 1.94 [1.10-3.43]).
The interest of FGF23 lies in its early-onset in the primary course of CKD as well as in the incremental prognosis information it conveys in both CKD and HF.
After multivariable adjustment for clinical variables and renal and CV biomarkers (estimated glomerular filtration rate, cystatin-C, urine albumin-to-creatinine ratio, FGF-23, high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein), low Klotho concentration remained strongly associated with increased risk of CV death or hospitalization for heart failure [adjusted hazard ratio (HR) 2.62; 95% confidence interval (CI) 1.35-5.08; P < 0.01].
Earlier studies adjusted for CKD-mineral bone disease (CKD-MBD) regulators of FGF23 rather than for recently discovered non-CKD-MBD regulators, among which iron deficiency and heart failure are of particular importance.
We evaluated single-nucleotide polymorphisms (SNPs) in FGF23, KL, and FGFR4 as the key exposures of interest in proportional hazards (Cox) regression models using adjudicated endpoints (all-cause and cardiovascular mortality, sudden cardiac death, and heart failure [HF]) as the outcomes of interest.
When analyses were stratified by patient sex, the association between FGF-23 and CV risk, including CV death or heart failure, appeared to be attenuated in women (adjusted HR, 1.11; 95% CI, 0.70-1.76; P = .67) compared with men (HR, 3.11; 95% CI, 2.29-4.22; P < .001; P < .001 for interaction).
Whether the FGF -23 association with HF is similar for heart failure with reduced ejection fraction ( HF r EF ) and heart failure with preserved ejection fraction ( HF p EF ) is not well established.
Higher circulating fibroblast growth factor 23 (FGF23) concentrations are associated with cardiovascular disease events linked to heart failure, but associations of FGF23 with coronary heart disease (CHD) have been less consistent.
Levels of fibroblast growth factor 23 (FGF23) increase early in chronic kidney disease (CKD) and are independently associated with left ventricular hypertrophy (LVH), heart failure and death.
Recent studies indicate that FGF23 is also expressed in the heart, and markedly enhanced in various clinical and experimental settings of cardiac remodeling and heart failure independent of preserved or reduced renal function.
We determined intact FGF-23 in HF patients with reduced ejection fraction and assess its prognosis value for cardiovascular death over a long-term follow-up.
Overall, comparing participants in the top and bottom FGF-23 concentration thirds, the summary RRs (95% confidence intervals [95% CIs]) were 1.33 (1.12 to 1.58) for myocardial infarction, 1.26 (1.13 to 1.41) for stroke, 1.48 (1.29 to 1.69) for heart failure, 1.42 (1.27 to 1.60) for cardiovascular mortality, and 1.70 (1.52 to 1.91) for all-cause mortality.
In patients with new-onset and worsening HF, higher plasma FGF23 levels were independently associated with volume overload, less successful uptitration of ACEi/ARBs and an increased risk of all-cause mortality and HF hospitalization.
The reported association of FGF23 levels with left ventricular hypertrophy (LVH) and heart failure observed in cohort studies may support the idea of adding the 4th component of CKD-MBD, namely, "LVH" to the three original components.
These findings suggested that serum FGF23 levels are predominantly correlated with clinical outcomes, may serve as a biomarker for HF in patients with higher RA pressure, may provide beneficial information for patients with right-sided HF and may represent different clinical information than that provided only by plasma BNP levels.
These findings suggest that diuretic use is a non-negligible confounder in understanding the observed association between SUA and cardiac dysfunction and heart failure.In summary, SUA is associated with left ventricular hypertrophy independent of confounding factors including FGF23 and diuretic use in female and male patients.
We noted that myocardial and plasma FGF23 and FGF receptor 4 were increased in mice with heart failure as well as in cultured adult mouse cardiac fibroblasts (AMCFs) exposed to angiotensin II, phenylephrine, soluble fractalkine.