Fibroblast Growth Factor-23, Heart Failure Risk, and Renin-Angiotensin-Aldosterone-System Blockade in Hypertension: The MESA Study

Ehimare Akhabue*, Thanh Huyen T. Vu, Anand Vaidya, Erin D. Michos, Ian H. De Boer, Bryan Kestenbaum, Matthew Allison, Moyses Szklo, Pamela Ouyang, Clyde W. Yancy, Myles Wolf, Tamara Isakova, Mercedes R. Carnethon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


BACKGROUND Higher fibroblast growth factor-23 (FGF23) concentrations have been found to be associated with incident heart failure (HF). Experimental data suggest FGF23 directly stimulates myocardial hypertrophy. FGF23 may also enhance renin-angiotensin-aldosterone system activity. Whether FGF23 is associated with increased HF risk in populations with hypertension and whether this association is weaker in the presence of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy is unknown. METHODS We studied 2,858 adults with hypertension free of cardiovascular disease at baseline (65.6 ± 9.5 years, 46.2% male) participating in the Multi-Ethnic Study of Atherosclerosis (MESA). We investigated the association of baseline serum intact FGF23 with incident HF over a 14-year median follow-up and whether ACEI/ARB therapy modified this risk. We also investigated the relationship of FGF23 with aldosterone and plasma renin activity in a random subgroup of the entire MESA cohort with available assays (N = 1,642). RESULTS In adjusted Cox regression models, higher FGF23 was associated with a 63% greater hazard of incident HF (hazard ratio: 1.63, 95% confidence interval: [1.13-2.36] per 1-unit increase in log-transformed FGF23), which persisted after exclusion of participants with chronic kidney disease (hazard ratio: 1.94 [1.10-3.43]). There was no heterogeneity by ACEI/ARB use (P interaction = 0.438). FGF23 improved model fit over covariables (likelihood ratio ‡ 2 = 6.67, P = 0.010). In multivariable linear regression models, there was no association between FGF23 and aldosterone or plasma renin activity. CONCLUSIONS Higher FGF23 concentrations are associated with a significantly increased risk of HF in hypertension but this risk did not differ by ACEI/ARB treatment status. FGF23 may be a useful biomarker for HF risk in hypertensive populations.

Original languageEnglish (US)
Pages (from-to)18-25
Number of pages8
JournalAmerican Journal of Hypertension
Issue number1
StatePublished - Jan 1 2019


  • aldosterone
  • angiotensin receptor antagonists
  • angiotensin-converting enzyme inhibitors
  • blood pressure
  • fibroblast growth factor 23
  • heart failure
  • hypertension
  • renin
  • renin-angiotensin system

ASJC Scopus subject areas

  • Internal Medicine


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