Association of FGF23 with Incident Sepsis in Community-Dwelling Adults: A Cohort Study

Background: Fibroblast 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. Methods: We 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 ≥2 Systemic Inflammatory Response Syndrome (SIRS) 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, estimated glomerular filtration rate, urine albumin to creatinine ratio and high sensitivity C-reactive protein. We also examined whether associations differed by age, race, sex and CKD by testing interaction terms. Results: Higher FG23 concentrations were associated with greater risk of sepsis (hazard ratio [HR] per doubling of FGF23 1.37, 95%CI 1.22,1.54) in models adjusted for socio-demographic and clinical variables. After further adjusting for estimated glomerular filtration rate, urine albumin to creatinine ratio and high sensitivity C-reactive protein, the association was attenuated and no longer statistically significant (HR per doubling 1.01, 95%CI 0.85,1.21). The results did not statistically differ by strata of age, sex, race, or CKD. Conclusions: In community-dwelling adults, higher FGF23 concentrations were not independently associated with higher risk of sepsis.