Urinary Potassium Excretion, Fibroblast Growth Factor 23, and Incident Hypertension in the General Population-Based PREVEND Cohort

Abstract

High plasma fibroblast growth factor 23 (FGF23) and low potassium intake have each been associated with incident hypertension. We recently demonstrated that potassium supplementation reduces FGF23 levels in pre-hypertensive individuals. The aim of the current study was to address whether 24-h urinary potassium excretion, reflecting dietary potassium intake, is associated with FGF23, and whether FGF23 mediates the association between urinary potassium excretion and incident hypertension in the general population. At baseline, 4194 community-dwelling individuals without hypertension were included. Mean urinary potassium excretion was 76 (23) mmol/24 h in men, and 64 (20) mmol/24 h in women. Plasma C-terminal FGF23 was 64.5 (54.2-77.8) RU/mL in men, and 70.3 (56.5-89.5) RU/mL in women. Urinary potassium excretion was inversely associated with FGF23, independent of age, sex, urinary sodium excretion, bone and mineral parameters, inflammation, and iron status (St. β -0.02, p < 0.05). The lowest sex-specific urinary potassium excretion tertile (HR 1.18 (95% CI 1.01-1.37)), and the highest sex-specific tertile of FGF23 (HR 1.17 (95% CI 1.01-1.37)) were each associated with incident hypertension, compared with the reference tertile. FGF23 did not mediate the association between urinary potassium excretion and incident hypertension. Increasing potassium intake, and reducing plasma FGF23 could be independent targets to reduce the risk of hypertension in the general population.

Keywords: FGF23; diet; epidemiology; hypertension; potassium.

Figure 1

Associations between urinary potassium excretion and incident hypertension in 3720 participants. Data were fit by a Cox proportional hazards regression model adjusted for age, BMI, eGFR, urinary sodium excretion, urinary albumin-to-creatinine ratio, smoking status, alcohol consumption, diabetes, history of cardiovascular disease, anti-diabetic, and lipid lowering drugs. The grey area represents the 95% CI. Abbreviations: eGFR, estimated glomerular filtration rate; BMI, body mass index.

Figure 2

Associations between fibroblast growth factor 23 and incident hypertension in 3720 participants. Data were fit by a Cox proportional hazards regression model adjusted for age, BMI, eGFR, urinary sodium excretion, urinary albumin-to-creatinine ratio, diabetes, smoking, history of cardiovascular disease, anti-diabetic, lipid lowering drugs, PTH, vitamin D, plasma phosphate, plasma corrected calcium, and urinary phosphate excretion. The grey area represents the 95% CI. Abbreviations: eGFR, estimated glomerular filtration rate; BMI, body mass index; PTH, parathyroid hormone.