Serum Fibroblast Growth Factor-23 and Incident Hypertension: the Atherosclerosis Risk in Communities (ARIC) Study

Objective: Elevated serum fibroblast growth factor-23 (FGF23), an endogenous hormone, is associated with disturbed mineral homeostasis, cardiovascular disease, and chronic kidney disease. It is unclear whether FGF23 impacts the development of incident hypertension. We examined the association between elevated FGF23 and incident hypertension in a community-based cohort.

Method: We investigated the association of serum FGF23, measured at baseline (1990-1992), with incident hypertension at two follow-up visits (1993-1995 and 1996-1998) in 7948 middle-aged men and women without hypertension at baseline participating in the Atherosclerosis Risk in Communities Study. Incident hypertension was determined by measured blood pressure (DBP ≥ 90 mmHg or SBP ≥ 140 mmHg) and/or self-reported hypertension medication use at follow-up exams. Complementary log-log models that accounted for interval censoring were used to model the association between FGF23 and incident hypertension.

Results: During a median follow-up of 5.9 years, 27% (2152/7948) participants developed hypertension. A nonlinear association between serum FGF23 and incident hypertension was observed; only persons in the highest decile of serum FGF23 had an increased risk of incident hypertension. After adjustment for demographics, behaviors, and adiposity, the hazard ratio for incident hypertension was 1.24 (95% confidence interval: 1.11, 1.39) for the highest decile of FGF23 compared with the lowest quintile. The association was further attenuated in the final model after adjusting for renal function (hazard ratio: 1.21, 95% confidence interval: 1.08, 1.35).

Conclusion: High levels (≥60.6 pg/ml) of FGF23 are associated with a modestly increased risk of incident hypertension in the general population, independent of kidney function.