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

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.

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Fibroblast growth factor 23, left ventricular mass, and left ventricular hypertrophy in community-dwelling older adults

Atherosclerosis ◽

10.1016/j.atherosclerosis.2013.09.002 ◽

2013 ◽

Vol 231 (1) ◽

pp. 114-119 ◽

Cited By ~ 50

Author(s):

Anna Jovanovich ◽

Joachim H. Ix ◽

John Gottdiener ◽

Kim McFann ◽

Ronit Katz ◽

...

Keyword(s):

Older Adults ◽

Growth Factor ◽

Left Ventricular Hypertrophy ◽

Fibroblast Growth Factor ◽

Ventricular Hypertrophy ◽

Fibroblast Growth Factor 23 ◽

Left Ventricular ◽

Community Dwelling ◽

Fibroblast Growth ◽

Community Dwelling Older Adults

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Abstract P050: Serum Fibroblast Growth Factor 23 and Incident Hypertension: The Atherosclerosis Risk in Communities Study

Circulation ◽

10.1161/circ.129.suppl_1.p050 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Amber L Fyfe-Johnson ◽

Alvaro Alonso ◽

Elizabeth Selvin ◽

Sunil K Agarwal ◽

James S Pankow ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 23 ◽

Elevated Serum ◽

Interval Censoring ◽

Fibroblast Growth ◽

Incident Hypertension ◽

Increased Risk ◽

Wall Stiffness

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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Elevated fibroblast growth factor-23 and risk of cardiovascular disease or mortality in the general population: A meta-analysis

International Journal of Cardiology ◽

10.1016/j.ijcard.2016.07.276 ◽

2016 ◽

Vol 222 ◽

pp. 342-345 ◽

Cited By ~ 4

Author(s):

Menglin Jiang ◽

Dandan Gong ◽

Yu Fan

Keyword(s):

Cardiovascular Disease ◽

Growth Factor ◽

General Population ◽

Fibroblast Growth Factor ◽

Meta Analysis ◽

Fibroblast Growth Factor 23 ◽

Fibroblast Growth

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Relationship of serum fibroblast growth factor 23 with cardiovascular disease in older community-dwelling women

Acta Endocrinologica ◽

10.1530/eje-11-0577 ◽

2011 ◽

Vol 165 (5) ◽

pp. 797-803 ◽

Cited By ~ 36

Author(s):

Mansi Dalal ◽

Kai Sun ◽

Anne R Cappola ◽

Luigi Ferrucci ◽

Candace Crasto ◽

...

Keyword(s):

Cardiovascular Disease ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 23 ◽

Elevated Serum ◽

Community Dwelling ◽

Fibroblast Growth ◽

Multivariable Logistic Regression Model ◽

Cross Sectional ◽

The Relationship

ObjectiveAlthough fibroblast growth factor 23 (FGF23) has been implicated in the pathogenesis of cardiovascular disease, the relationship between FGF23 and cardiovascular disease has not been well characterized in the general population. The aim of this study was to determine whether serum FGF23 is independently associated with cardiovascular disease in older community-dwelling women.Design and methodsA cross-sectional design was used to examine the relationship between serum FGF23 and cardiovascular disease. The subjects consisted of a population-based sample of 659 women, aged 70–79 years, who participated in the Women's Health and Aging Studies in Baltimore, Maryland. Prevalent cardiovascular disease (coronary heart disease, stroke, congestive heart failure, and peripheral artery disease) was assessed through diagnostic algorithms and physician adjudication.ResultsOf the 659 women, 185 (28.1%) had cardiovascular disease. Median (25th, 75th percentile) intact serum FGF23 was 34.6 (25.2, 46.2) pg/ml. The prevalence of cardiovascular disease in the lowest, middle, and highest tertile of serum FGF23 was 22.6, 24.9, and 36.7% respectively (P=0.002). Serum log FGF23 was associated with cardiovascular disease (odds ratio per 1s.d.increase=1.23, 95% confidence interval 1.17, 1.30;P<0.0001) in a multivariable logistic regression model, adjusting for age, race, smoking, education, body mass index, cognition, diabetes, hypertension, physical activity, total cholesterol, high-density lipoprotein cholesterol, and renal function.ConclusionElevated serum FGF23 concentrations are independently associated with prevalent cardiovascular disease in older community-dwelling women. Further studies are needed to elucidate the potential biological mechanisms by which FGF23 may be involved in the pathogenesis of cardiovascular disease.

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