Fibroblast growth factor 23, the ankle-brachial index, and incident peripheral artery disease in the Cardiovascular Health Study

Pranav S. Garimella, Joachim H. Ix, Ronit Katz, Michel B. Chonchol, Bryan R. Kestenbaum, Ian H. de Boer, David S. Siscovick, Shani Shastri, Jade S. Hiramoto, Michael G. Shlipak, Mark J. Sarnak

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: Fibroblast growth factor 23 (FGF23) has emerged as a novel risk factor for mortality and cardiovascular events. Its association with the ankle-brachial index (ABI) and clinical peripheral artery disease (PAD) is less known. Methods: Using data (N=3143) from the Cardiovascular Health Study (CHS), a cohort of community dwelling adults >65 years of age, we analyzed the cross-sectional association of FGF23 with ABI and its association with incident clinical PAD events during 9.8 years of follow up using multinomial logistic regression and Cox proportional hazards models respectively. Results: The prevalence of cardiovascular disease (CVD) and traditional risk factors like diabetes, coronary artery disease, and heart failure increased across higher quartiles of FGF23. Compared to those with ABI of 1.1-1.4, FGF23 per doubling at baseline was associated with prevalent PAD (ABI<0.9) although this association was attenuated after adjusting for CVD risk factors, and kidney function (OR 0.91, 95% CI 0.76-1.08). FGF23 was not associated with high ABI (>1.4) (OR 1.06, 95% CI 0.75-1.51). Higher FGF23 was associated with incidence of PAD events in unadjusted, demographic adjusted, and CVD risk factor adjusted models (HR 2.26, 95% CI 1.28-3.98; highest versus lowest quartile). The addition of estimated glomerular filtration and urine albumin to creatinine ratio to the model however, attenuated these findings (HR 1.46, 95% CI, 0.79-2.70). Conclusions: In community dwelling older adults, FGF23 was not associated with baseline low or high ABI or incident PAD events after adjusting for confounding variables. These results suggest that FGF23 may primarily be associated with adverse cardiovascular outcomes through non atherosclerotic mechanisms.

Original languageEnglish (US)
Pages (from-to)91-96
Number of pages6
JournalAtherosclerosis
Volume233
Issue number1
DOIs
StatePublished - Mar 2014

Fingerprint

Ankle Brachial Index
Peripheral Arterial Disease
Health
Independent Living
Cardiovascular Diseases
Confounding Factors (Epidemiology)
fibroblast growth factor 23
Proportional Hazards Models
Coronary Artery Disease
Albumins
Creatinine
Cohort Studies
Heart Failure
Logistic Models
Demography
Urine
Mortality
Incidence

Keywords

  • Ankle-brachial index
  • Cardiovascular disease
  • Chronic kidney disease
  • Fibroblast growth factor
  • Peripheral artery disease

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Garimella, P. S., Ix, J. H., Katz, R., Chonchol, M. B., Kestenbaum, B. R., de Boer, I. H., ... Sarnak, M. J. (2014). Fibroblast growth factor 23, the ankle-brachial index, and incident peripheral artery disease in the Cardiovascular Health Study. Atherosclerosis, 233(1), 91-96. https://doi.org/10.1016/j.atherosclerosis.2013.12.015

Fibroblast growth factor 23, the ankle-brachial index, and incident peripheral artery disease in the Cardiovascular Health Study. / Garimella, Pranav S.; Ix, Joachim H.; Katz, Ronit; Chonchol, Michel B.; Kestenbaum, Bryan R.; de Boer, Ian H.; Siscovick, David S.; Shastri, Shani; Hiramoto, Jade S.; Shlipak, Michael G.; Sarnak, Mark J.

In: Atherosclerosis, Vol. 233, No. 1, 03.2014, p. 91-96.

Research output: Contribution to journalArticle

Garimella, PS, Ix, JH, Katz, R, Chonchol, MB, Kestenbaum, BR, de Boer, IH, Siscovick, DS, Shastri, S, Hiramoto, JS, Shlipak, MG & Sarnak, MJ 2014, 'Fibroblast growth factor 23, the ankle-brachial index, and incident peripheral artery disease in the Cardiovascular Health Study', Atherosclerosis, vol. 233, no. 1, pp. 91-96. https://doi.org/10.1016/j.atherosclerosis.2013.12.015
Garimella, Pranav S. ; Ix, Joachim H. ; Katz, Ronit ; Chonchol, Michel B. ; Kestenbaum, Bryan R. ; de Boer, Ian H. ; Siscovick, David S. ; Shastri, Shani ; Hiramoto, Jade S. ; Shlipak, Michael G. ; Sarnak, Mark J. / Fibroblast growth factor 23, the ankle-brachial index, and incident peripheral artery disease in the Cardiovascular Health Study. In: Atherosclerosis. 2014 ; Vol. 233, No. 1. pp. 91-96.
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abstract = "Background: Fibroblast growth factor 23 (FGF23) has emerged as a novel risk factor for mortality and cardiovascular events. Its association with the ankle-brachial index (ABI) and clinical peripheral artery disease (PAD) is less known. Methods: Using data (N=3143) from the Cardiovascular Health Study (CHS), a cohort of community dwelling adults >65 years of age, we analyzed the cross-sectional association of FGF23 with ABI and its association with incident clinical PAD events during 9.8 years of follow up using multinomial logistic regression and Cox proportional hazards models respectively. Results: The prevalence of cardiovascular disease (CVD) and traditional risk factors like diabetes, coronary artery disease, and heart failure increased across higher quartiles of FGF23. Compared to those with ABI of 1.1-1.4, FGF23 per doubling at baseline was associated with prevalent PAD (ABI<0.9) although this association was attenuated after adjusting for CVD risk factors, and kidney function (OR 0.91, 95{\%} CI 0.76-1.08). FGF23 was not associated with high ABI (>1.4) (OR 1.06, 95{\%} CI 0.75-1.51). Higher FGF23 was associated with incidence of PAD events in unadjusted, demographic adjusted, and CVD risk factor adjusted models (HR 2.26, 95{\%} CI 1.28-3.98; highest versus lowest quartile). The addition of estimated glomerular filtration and urine albumin to creatinine ratio to the model however, attenuated these findings (HR 1.46, 95{\%} CI, 0.79-2.70). Conclusions: In community dwelling older adults, FGF23 was not associated with baseline low or high ABI or incident PAD events after adjusting for confounding variables. These results suggest that FGF23 may primarily be associated with adverse cardiovascular outcomes through non atherosclerotic mechanisms.",
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AU - Ix, Joachim H.

AU - Katz, Ronit

AU - Chonchol, Michel B.

AU - Kestenbaum, Bryan R.

AU - de Boer, Ian H.

AU - Siscovick, David S.

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AU - Hiramoto, Jade S.

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KW - Chronic kidney disease

KW - Fibroblast growth factor

KW - Peripheral artery disease

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