Fibroblast Growth Factor 23 and Incident Cardiovascular Disease and Mortality in Middle‐Aged Adults

Abstract

Background Higher circulating fibroblast growth factor 23 (FGF23) associates with greater risk of cardiovascular disease (CVD) and mortality in older adults. The association of FGF23 with cardiovascular outcomes in younger populations has been incompletely explored. Methods and Results We measured C‐terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) in 3151 middle‐aged adults (mean age, 45±4) who participated in the year 20 examination of the CARDIA (Coronary Artery Risk Development in Young Adults) study. We used separate Cox proportional hazards models to examine the associations of cFGF23 and iFGF23 with incident CVD and mortality, adjusting models sequentially for sociodemographic, clinical, and laboratory factors. A total of 157 incident CVD events and 135 deaths occurred over a median 7.6 years of follow‐up (interquartile range, 4.1–9.9). In fully adjusted models, there were no statistically significant associations of FGF23 with incident CVD events (hazard ratio per doubling of cFGF23: 1.14, 95%CI 0.97,1.34; iFGF23: 0.76, 95%CI 0.57,1.02) or all‐cause mortality (hazard ratio per doubling of cFGF23, 1.17; 95% CI, 1.00–1.38; iFGF23, 0.86; 95% CI, 0.64–1.17). In analyses stratified by CVD subtypes, higher cFGF23 was associated with greater risk of heart failure hospitalization (hazard ratio per doubling of cFGF23, 1.52; 95% CI, 1.18–1.96) but not coronary heart disease or stroke, whereas iFGF23 was not associated with CVD subtypes in any model. Conclusions In middle‐aged adults with few comorbidities, higher cFGF23 and iFGF23 were not independently associated with greater risk of CVD events or death. Higher cFGF23 was independently associated with greater risk of heart failure hospitalization.

Targeted plasma proteomics reveals upregulation of distinct inflammatory pathways in people living with HIV

“…Furthermore, FGF-23, OSM, CCL19, SLAMF1, and HGF consistently showed positive associations with CVD events in PLHIV, both at baseline and during a 5-year follow-up ( Figure S10 ), confirming the well-established link of sustained inflammation in PLHIV under suppressive ART with an increased CVD risk ( Freiberg et al., 2013 ; Nordell et al., 2014 ). Previous studies have highlighted the relation of these proteins with the pathophysiology ( Cai et al., 2014 ; Kubin et al., 2011 ) and the incidence of CVD ( Bell et al., 2016 , 2018 ; Bielinski et al., 2017 ; Ferreira et al., 2019 ; Gruson et al., 2017 ; Ikeda et al., 2021 ; Ix Joachim et al., 2012 ; Paul et al., 2021 ; Vázquez-Sánchez et al., 2021 ) in the general population and PLHIV ( Atta et al., 2016 ; Domingo et al., 2015 ; García-Broncano et al., 2014 ). In addition, OSM receptor has been reported to be associated with the presence of coronary calcium, independent from traditional atherosclerotic CVD risk, in PLHIV on ART ( Kolossváry et al., 2022 ).…”

Fibroblast growth factor-23 and the risk of cardiovascular diseases and mortality in the general population: A systematic review and dose-response meta-analysis

“…The categorical analysis revealed that high FGF23 levels were related to increased risk of MI (RR: 1.40, 95%CI:1.03−1.89, p = 0.03; Figure 2A), with low heterogeneity (p = 0.31, I 2 = 2%). Four studies reported continuous analysis (23)(24)(25)(26); the RR of MI Six studies analyzed the relationship between FGF23 levels and stroke (23,24,(27)(28)(29)(30). High FGF23 levels were related to increased risk of stroke in the categorical analysis (RR: 1.20, 95%CI: 1.02−1.43, p = 0.03; Figure 2C), without heterogeneity (p = 0.66, I 2 = 0%).…”

“…High FGF23 levels were related to increased risk of stroke in the categorical analysis (RR: 1.20, 95%CI: 1.02−1.43, p = 0.03; Figure 2C), without heterogeneity (p = 0.66, I 2 = 0%). In the continuous analysis, the RR of stroke per doubling of FGF23 was 1.21 (95%CI: 0.99−1.48, p = 0.06; Moreover, six studies performed a dose-response analysis (23,24,(27)(28)(29)(30), revealing a non-linear association between FGF23 and stroke (p for non-linearity = 0.10; Figure 3A).…”

“…Ten studies (24)(25)(26)(27)(30)(31)(32)(33)(34)(35) reported the association between FGF23 levels and HF in general populations. A significant increase in HF risk was associated with high FGF23 levels (RR: 1.37, 95%CI: 1.23−1.52, p < 0.00001; Figure 2E), without heterogeneity (p = 0.92, I 2 = 0%).…”

Fibroblast Growth Factor 23 and Outcome Prediction in Patients with Acute Myocardial Infarction

“…Likewise, elevated FGF23 had stronger associations with chronic HF than with atherosclerotic events (including MI, stroke, and peripheral vascular disease) in a prospective cohort of CKD [15], and data from the community-based Framingham Heart Study showed that FGF23 was positively associated with all-cause mortality but not with vascular function or incident cardiovascular disease [16]. A recent study investigating FGF23 and cardiovascular outcomes in a younger (aged 45 ± 4 years) patient cohort with few comorbidities found no associations between FGF23 and incident CAD, CAD events, and mortality, whereas elevated FGF23 was independently associated with a greater risk of hospitalization for HF [17].…”