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.

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BackgroundFibroblast growth factor 23 (FGF23) is a hormone that regulates vitamin D activity. Higher circulating FGF23 concentrations have been associated with an increased risk of infection-related hospitalization, but the association of FGF23 with risk of sepsis remains unclear.MethodsWe examined the association of FGF23 with incident sepsis events in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national longitudinal cohort of black and white adults ≥45 years of age. Using a case-cohort design, we measured baseline FGF23 in 703 sepsis cases and in 991 participants randomly selected from the REGARDS cohort. We defined sepsis as the presence of a serious infection plus two or more Systemic Inflammatory Response Syndrome criteria. We identified first sepsis hospitalizations during 2003–2012 by adjudicated medical record review. Cox proportional hazards models were used to examine associations of FGF23 with incident sepsis, adjusting for age, sex, race, income, education, smoking, body mass index, physical activity, chronic pulmonary disease, eGFR, urine albumin-creatinine ratio, and high-sensitivity C-reactive protein. We also examined whether associations differed by age, race, sex, and CKD by testing interaction terms.ResultsHigher FG23 concentrations were associated with greater risk of sepsis (hazard ratio [HR] per doubling of FGF23, 1.37; 95% CI, 1.22 to 1.54) in models adjusted for sociodemographic and clinical variables. After further adjusting for eGFR, urine albumin-creatinine ratio, and high-sensitivity C-reactive protein, the association was attenuated and no longer statistically significant (HR per doubling, 1.01; 95% CI, 0.85 to 1.21). The results did not statistically differ by strata of age, sex, race, or CKD.ConclusionsIn community-dwelling adults, higher FGF23 concentrations were not independently associated with higher risk of sepsis.