The fibroblast growth factor-23 and Vitamin D emerge as nontraditional risk factors and may affect cardiovascular risk

S. Masson, N. Agabiti, T. Vago, M. Miceli, F. Mayer, T. Letizia, U. Wienhues-Thelen, G. F. Mureddu, M. Davoli, A. Boccanelli, R. Latini

Research output: Contribution to journalArticle

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Abstract

Objectives: Fibroblast growth factor-23 (FGF-23) and vitamin D are hormones involved in phosphate homoeostasis. They also directly influence cardiomyocyte hypertrophy. We examined whether the relationships between levels of vitamin D or FGF-23, cardiac phenotype and outcome were independent of established cardiac biomarkers in a large cohort of community-dwelling elderly subjects. Design and Setting: Plasma levels of FGF-23 and vitamin D were measured in 1851 men and women (65-84 years) resident in the Lazio region of Italy. Participants were referred to eight cardiology centres for clinical examination, electrocardiography, comprehensive Doppler echocardiography and blood sampling. All-cause mortality or hospitalizations were available after a median follow-up of 47 months with record linkage of administrative data. Results: Vitamin D deficiency (-1) was found in 72.3% of subjects, but FGF-23 levels were normal [74 (58-97) RU per mL]. After adjustment for cardiovascular risk factors and morbidities, low concentrations of vitamin D and high levels of FGF-23 were associated with a higher left ventricular (LV) mass index. Levels of FGF-23 [hazard ratio (HR) (95% confidence interval (CI)) 1.71 (1.28-2.28), P <0.0001] but not vitamin D [0.76 (0.57-1.01), P = 0.08] were independently associated with mortality after adjustment for clinical risk factors and two cardiac markers together (N-terminal pro-brain natriuretic peptide and high-sensitivity cardiac troponin T), but did not predict hospital admission. People with above median values of FGF-23 and below median values of vitamin D had greater LV hypertrophy and higher mortality. Conclusions: In community-dwelling elderly individuals with highly prevalent vitamin D deficiency, FGF-23 levels were associated with LV hypertrophy and predicted mortality independently of two robust cardiac biomarkers. A causal relationship was not demonstrated, but the hormones involved in mineral metabolism emerged as nontraditional risk factors and may affect cardiovascular risk.

Original languageEnglish
Pages (from-to)318-330
Number of pages13
JournalJournal of Internal Medicine
Volume277
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

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Vitamin D
Independent Living
Vitamin D Deficiency
Mortality
Left Ventricular Hypertrophy
Biomarkers
Hormones
Troponin T
fibroblast growth factor 23
Doppler Echocardiography
Brain Natriuretic Peptide
Information Storage and Retrieval
Cardiology
Cardiac Myocytes
Hypertrophy
Italy
Minerals
Electrocardiography
Hospitalization
Homeostasis

Keywords

  • Community
  • Elderly
  • Fibroblast growth factor-23
  • Left ventricular mass
  • Prognosis
  • Vitamin D

ASJC Scopus subject areas

  • Internal Medicine
  • Medicine(all)

Cite this

The fibroblast growth factor-23 and Vitamin D emerge as nontraditional risk factors and may affect cardiovascular risk. / Masson, S.; Agabiti, N.; Vago, T.; Miceli, M.; Mayer, F.; Letizia, T.; Wienhues-Thelen, U.; Mureddu, G. F.; Davoli, M.; Boccanelli, A.; Latini, R.

In: Journal of Internal Medicine, Vol. 277, No. 3, 01.03.2015, p. 318-330.

Research output: Contribution to journalArticle

Masson, S, Agabiti, N, Vago, T, Miceli, M, Mayer, F, Letizia, T, Wienhues-Thelen, U, Mureddu, GF, Davoli, M, Boccanelli, A & Latini, R 2015, 'The fibroblast growth factor-23 and Vitamin D emerge as nontraditional risk factors and may affect cardiovascular risk', Journal of Internal Medicine, vol. 277, no. 3, pp. 318-330. https://doi.org/10.1111/joim.12232
Masson, S. ; Agabiti, N. ; Vago, T. ; Miceli, M. ; Mayer, F. ; Letizia, T. ; Wienhues-Thelen, U. ; Mureddu, G. F. ; Davoli, M. ; Boccanelli, A. ; Latini, R. / The fibroblast growth factor-23 and Vitamin D emerge as nontraditional risk factors and may affect cardiovascular risk. In: Journal of Internal Medicine. 2015 ; Vol. 277, No. 3. pp. 318-330.
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abstract = "Objectives: Fibroblast growth factor-23 (FGF-23) and vitamin D are hormones involved in phosphate homoeostasis. They also directly influence cardiomyocyte hypertrophy. We examined whether the relationships between levels of vitamin D or FGF-23, cardiac phenotype and outcome were independent of established cardiac biomarkers in a large cohort of community-dwelling elderly subjects. Design and Setting: Plasma levels of FGF-23 and vitamin D were measured in 1851 men and women (65-84 years) resident in the Lazio region of Italy. Participants were referred to eight cardiology centres for clinical examination, electrocardiography, comprehensive Doppler echocardiography and blood sampling. All-cause mortality or hospitalizations were available after a median follow-up of 47 months with record linkage of administrative data. Results: Vitamin D deficiency (-1) was found in 72.3{\%} of subjects, but FGF-23 levels were normal [74 (58-97) RU per mL]. After adjustment for cardiovascular risk factors and morbidities, low concentrations of vitamin D and high levels of FGF-23 were associated with a higher left ventricular (LV) mass index. Levels of FGF-23 [hazard ratio (HR) (95{\%} confidence interval (CI)) 1.71 (1.28-2.28), P <0.0001] but not vitamin D [0.76 (0.57-1.01), P = 0.08] were independently associated with mortality after adjustment for clinical risk factors and two cardiac markers together (N-terminal pro-brain natriuretic peptide and high-sensitivity cardiac troponin T), but did not predict hospital admission. People with above median values of FGF-23 and below median values of vitamin D had greater LV hypertrophy and higher mortality. Conclusions: In community-dwelling elderly individuals with highly prevalent vitamin D deficiency, FGF-23 levels were associated with LV hypertrophy and predicted mortality independently of two robust cardiac biomarkers. A causal relationship was not demonstrated, but the hormones involved in mineral metabolism emerged as nontraditional risk factors and may affect cardiovascular risk.",
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AU - Mayer, F.

AU - Letizia, T.

AU - Wienhues-Thelen, U.

AU - Mureddu, G. F.

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