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 Donnelly Michos, Ian H. de Boer, Bryan Kestenbaum, Matthew Allison, Moyses Szklo, Pamela Ouyang, Clyde W. Yancy, Myles Wolf, Tamara Isakova, Mercedes R. Carnethon

Research output: Contribution to journalArticle

Abstract

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 (Pinteraction = 0.438). FGF23 improved model fit over covariables (likelihood ratio χ2 = 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
Volume32
Issue number1
DOIs
StatePublished - Jan 1 2019

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Renin-Angiotensin System
Atherosclerosis
Heart Failure
Hypertension
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Aldosterone
Renin
fibroblast growth factor 23
Linear Models
Chronic Renal Insufficiency
Proportional Hazards Models
Hypertrophy
Population
Cohort Studies
Cardiovascular Diseases
Biomarkers
Confidence Intervals

ASJC Scopus subject areas

  • Internal Medicine

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Fibroblast Growth Factor-23, Heart Failure Risk, and Renin-Angiotensin-Aldosterone-System Blockade in Hypertension : The MESA Study. / Akhabue, Ehimare; Vu, Thanh Huyen T.; Vaidya, Anand; Michos, Erin Donnelly; de Boer, Ian H.; Kestenbaum, Bryan; Allison, Matthew; Szklo, Moyses; Ouyang, Pamela; Yancy, Clyde W.; Wolf, Myles; Isakova, Tamara; Carnethon, Mercedes R.

In: American Journal of Hypertension, Vol. 32, No. 1, 01.01.2019, p. 18-25.

Research output: Contribution to journalArticle

Akhabue, E, Vu, THT, Vaidya, A, Michos, ED, de Boer, IH, Kestenbaum, B, Allison, M, Szklo, M, Ouyang, P, Yancy, CW, Wolf, M, Isakova, T & Carnethon, MR 2019, 'Fibroblast Growth Factor-23, Heart Failure Risk, and Renin-Angiotensin-Aldosterone-System Blockade in Hypertension: The MESA Study', American Journal of Hypertension, vol. 32, no. 1, pp. 18-25. https://doi.org/10.1093/ajh/hpy142
Akhabue, Ehimare ; Vu, Thanh Huyen T. ; Vaidya, Anand ; Michos, Erin Donnelly ; de Boer, Ian H. ; Kestenbaum, Bryan ; Allison, Matthew ; Szklo, Moyses ; Ouyang, Pamela ; Yancy, Clyde W. ; Wolf, Myles ; Isakova, Tamara ; Carnethon, Mercedes R. / Fibroblast Growth Factor-23, Heart Failure Risk, and Renin-Angiotensin-Aldosterone-System Blockade in Hypertension : The MESA Study. In: American Journal of Hypertension. 2019 ; Vol. 32, No. 1. pp. 18-25.
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title = "Fibroblast Growth Factor-23, Heart Failure Risk, and Renin-Angiotensin-Aldosterone-System Blockade in Hypertension: The MESA Study",
abstract = "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 (Pinteraction = 0.438). FGF23 improved model fit over covariables (likelihood ratio χ2 = 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.",
author = "Ehimare Akhabue and Vu, {Thanh Huyen T.} and Anand Vaidya and Michos, {Erin Donnelly} and {de Boer}, {Ian H.} and Bryan Kestenbaum and Matthew Allison and Moyses Szklo and Pamela Ouyang and Yancy, {Clyde W.} and Myles Wolf and Tamara Isakova and Carnethon, {Mercedes R.}",
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T1 - Fibroblast Growth Factor-23, Heart Failure Risk, and Renin-Angiotensin-Aldosterone-System Blockade in Hypertension

T2 - The MESA Study

AU - Akhabue, Ehimare

AU - Vu, Thanh Huyen T.

AU - Vaidya, Anand

AU - Michos, Erin Donnelly

AU - de Boer, Ian H.

AU - Kestenbaum, Bryan

AU - Allison, Matthew

AU - Szklo, Moyses

AU - Ouyang, Pamela

AU - Yancy, Clyde W.

AU - Wolf, Myles

AU - Isakova, Tamara

AU - Carnethon, Mercedes R.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 (Pinteraction = 0.438). FGF23 improved model fit over covariables (likelihood ratio χ2 = 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.

AB - 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 (Pinteraction = 0.438). FGF23 improved model fit over covariables (likelihood ratio χ2 = 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.

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