Abstract

Background: Elevated serum fibroblast growth factor-23 (FGF23), an endogenous hormone, is associated with endothelial dysfunction, chronic kidney disease, arterial wall stiffness, and inflammation. These factors may contribute to an increased risk of hypertension. To date, the association of FGF23 with incident hypertension has not been examined. Hypothesis: Elevated serum FGF23 will be positively associated with risk of incident hypertension. Methods: The ARIC study measured intact FGF23 in stored serum from 7,948 middle-aged men and women without hypertension at baseline (1990-92). Participants were examined during two follow-up visits, in 1993-95 and 1996-98. Incident hypertension was determined by measured blood pressure (DBP 90 mm Hg, or SBP140 mm Hg) and/or hypertension medication use during the follow-up exams. Multivariate Cox proportional hazards regression models and complementary log-log models were used to adjust for potential confounding variables. Results: During a median follow-up of 5.9 years, 27% (2,152/7,948) participants developed hypertension. A nonlinear association between serum FGF23 and incident hypertension was observed; only the highest decile of serum FGF23 was positively associated with incident hypertension (Table). After adjustment for demographics, the hazard ratio for incident hypertension was 1.37 (95% CI: 1.17, 1.60) for the highest decile of FGF23 compared to the lowest quintile. After adjustment for behaviors and adiposity the HR was 1.25 (95% CI: 1.07, 1.46). The association was further attenuated in the final model after adjusting for renal function (HR: 1.20, 95% CI: 1.03, 1.41). Complementary log-log models that accounted for interval censoring did not alter results. Conclusions: High levels ( 60.6 pg/mL) of FGF23 are associated with a modestly increased risk of incident hypertension in the general population. Next steps include replication of these findings in other cohorts, and examining the association with a longer follow-up period.

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