Association of Fibroblast Growth Factor-23 (FGF-23) with Incident Frailty in HIV-Infected and HIV-Uninfected Individuals

Ruibin Wang, Michael G. Shlipak, Joachim H. Ix, Todd T. Brown, Lisa P. Jacobson, Frank Joseph Palella Jr, Jordan E. Lake, Susan L. Koletar, Richard D. Semba, Michelle M. Estrella

Research output: Contribution to journalArticle

Abstract

Background:In the Multicenter AIDS Cohort Study, we examined whether fibroblast growth factor-23 (FGF-23), a bone-derived phosphaturic hormone involved in bone metabolism, is associated with incident frailty. Furthermore, we examined whether this association differs by HIV serostatus and race.Methods:Of 715 men assessed for frailty and selected for FGF-23 measurements using stored blood samples (2007-2011), 512 men were nonfrail at/before the baseline visit. Frailty was defined by the presence of ≥3 of the following on 2 consecutive 6-month visits within 1 year: unintentional weight loss ≥10 pounds, weakness, slowness, low energy, and low physical activity. We determined the association of FGF-23 levels with incident frailty using proportional hazards models adjusting for sociodemographics, comorbidities, and kidney function.Results:Sixty-five percent were HIV-infected; 29% were black. Median baseline FGF-23 levels were lower in HIV-infected vs. HIV-uninfected men (33.7 vs. 39.9 rU/mL, P = 0.006) but similar by race. During a median follow-up of 6.6 years, 32 men developed frailty; they had higher baseline FGF-23 levels vs. men who remained nonfrail (45 vs. 36 rU/mL, P = 0.02). FGF-23 (per doubling) was associated with a 1.63-fold risk of frailty [95% confidence interval (CI): 1.19 to 2.23]; results did not differ by HIV serostatus. Conversely, FGF-23 was associated with a 2.72-fold risk of frailty among blacks (95% CI: 1.51 to 4.91) but had minimal association among nonblacks (hazard ratio = 1.26, 95% CI: 0.77 to 2.05; p-interaction = 0.024).Conclusions:Among men with or at-risk of HIV infection, higher FGF-23 was associated with greater risk of frailty, particularly in blacks. The mechanisms by which FGF-23 may contribute to frailty warrant further study.

Original languageEnglish (US)
Pages (from-to)118-125
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume80
Issue number1
DOIs
StatePublished - Jan 1 2019

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HIV
Confidence Intervals
fibroblast growth factor 23
Bone and Bones
Proportional Hazards Models
HIV Infections
Comorbidity
Weight Loss
Acquired Immunodeficiency Syndrome
Cohort Studies
Hormones
Exercise
Kidney

Keywords

  • FGF-23
  • HIV
  • frailty

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Wang, Ruibin ; Shlipak, Michael G. ; Ix, Joachim H. ; Brown, Todd T. ; Jacobson, Lisa P. ; Palella Jr, Frank Joseph ; Lake, Jordan E. ; Koletar, Susan L. ; Semba, Richard D. ; Estrella, Michelle M. / Association of Fibroblast Growth Factor-23 (FGF-23) with Incident Frailty in HIV-Infected and HIV-Uninfected Individuals. In: Journal of Acquired Immune Deficiency Syndromes. 2019 ; Vol. 80, No. 1. pp. 118-125.
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Association of Fibroblast Growth Factor-23 (FGF-23) with Incident Frailty in HIV-Infected and HIV-Uninfected Individuals. / Wang, Ruibin; Shlipak, Michael G.; Ix, Joachim H.; Brown, Todd T.; Jacobson, Lisa P.; Palella Jr, Frank Joseph; Lake, Jordan E.; Koletar, Susan L.; Semba, Richard D.; Estrella, Michelle M.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 80, No. 1, 01.01.2019, p. 118-125.

Research output: Contribution to journalArticle

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T1 - Association of Fibroblast Growth Factor-23 (FGF-23) with Incident Frailty in HIV-Infected and HIV-Uninfected Individuals

AU - Wang, Ruibin

AU - Shlipak, Michael G.

AU - Ix, Joachim H.

AU - Brown, Todd T.

AU - Jacobson, Lisa P.

AU - Palella Jr, Frank Joseph

AU - Lake, Jordan E.

AU - Koletar, Susan L.

AU - Semba, Richard D.

AU - Estrella, Michelle M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background:In the Multicenter AIDS Cohort Study, we examined whether fibroblast growth factor-23 (FGF-23), a bone-derived phosphaturic hormone involved in bone metabolism, is associated with incident frailty. Furthermore, we examined whether this association differs by HIV serostatus and race.Methods:Of 715 men assessed for frailty and selected for FGF-23 measurements using stored blood samples (2007-2011), 512 men were nonfrail at/before the baseline visit. Frailty was defined by the presence of ≥3 of the following on 2 consecutive 6-month visits within 1 year: unintentional weight loss ≥10 pounds, weakness, slowness, low energy, and low physical activity. We determined the association of FGF-23 levels with incident frailty using proportional hazards models adjusting for sociodemographics, comorbidities, and kidney function.Results:Sixty-five percent were HIV-infected; 29% were black. Median baseline FGF-23 levels were lower in HIV-infected vs. HIV-uninfected men (33.7 vs. 39.9 rU/mL, P = 0.006) but similar by race. During a median follow-up of 6.6 years, 32 men developed frailty; they had higher baseline FGF-23 levels vs. men who remained nonfrail (45 vs. 36 rU/mL, P = 0.02). FGF-23 (per doubling) was associated with a 1.63-fold risk of frailty [95% confidence interval (CI): 1.19 to 2.23]; results did not differ by HIV serostatus. Conversely, FGF-23 was associated with a 2.72-fold risk of frailty among blacks (95% CI: 1.51 to 4.91) but had minimal association among nonblacks (hazard ratio = 1.26, 95% CI: 0.77 to 2.05; p-interaction = 0.024).Conclusions:Among men with or at-risk of HIV infection, higher FGF-23 was associated with greater risk of frailty, particularly in blacks. The mechanisms by which FGF-23 may contribute to frailty warrant further study.

AB - Background:In the Multicenter AIDS Cohort Study, we examined whether fibroblast growth factor-23 (FGF-23), a bone-derived phosphaturic hormone involved in bone metabolism, is associated with incident frailty. Furthermore, we examined whether this association differs by HIV serostatus and race.Methods:Of 715 men assessed for frailty and selected for FGF-23 measurements using stored blood samples (2007-2011), 512 men were nonfrail at/before the baseline visit. Frailty was defined by the presence of ≥3 of the following on 2 consecutive 6-month visits within 1 year: unintentional weight loss ≥10 pounds, weakness, slowness, low energy, and low physical activity. We determined the association of FGF-23 levels with incident frailty using proportional hazards models adjusting for sociodemographics, comorbidities, and kidney function.Results:Sixty-five percent were HIV-infected; 29% were black. Median baseline FGF-23 levels were lower in HIV-infected vs. HIV-uninfected men (33.7 vs. 39.9 rU/mL, P = 0.006) but similar by race. During a median follow-up of 6.6 years, 32 men developed frailty; they had higher baseline FGF-23 levels vs. men who remained nonfrail (45 vs. 36 rU/mL, P = 0.02). FGF-23 (per doubling) was associated with a 1.63-fold risk of frailty [95% confidence interval (CI): 1.19 to 2.23]; results did not differ by HIV serostatus. Conversely, FGF-23 was associated with a 2.72-fold risk of frailty among blacks (95% CI: 1.51 to 4.91) but had minimal association among nonblacks (hazard ratio = 1.26, 95% CI: 0.77 to 2.05; p-interaction = 0.024).Conclusions:Among men with or at-risk of HIV infection, higher FGF-23 was associated with greater risk of frailty, particularly in blacks. The mechanisms by which FGF-23 may contribute to frailty warrant further study.

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