The Heart and Kidney: Abnormal Phosphate Homeostasis Is Associated With Atherosclerosis

Abstract

ContextPhosphate has gained recognition as a risk factor for adverse cardiovascular outcomes, potentially due to accelerated vascular calcification. Fibroblast growth factor-23 (FGF-23) is a counter-regulatory hormone that increases renal phosphate excretion to maintain normal levels.ObjectiveThe purpose of the study was to determine the association of phosphate and FGF-23 to atherosclerosis.Design and SettingA prospective cohort study (n = 204) of outpatients referred for coronary angiography over of a 1-year recruitment period at the Kingston General Hospital.InterventionBlood was collected, and a focused carotid ultrasound was performed.Main Outcome MeasureDegree of angiographic coronary artery disease was scored. Carotid maximum plaque height, total area, grayscale median, and tissue pixel distribution were measured. Plasma phosphate was assessed by mineral assay and FGF-23 by ELISA.ResultsCarotid plaque burden [total plaque area (TPA)] was associated with higher levels of phosphate (TPA, r = 0.20, P < 0.01) and FGF-23 (r = 0.19, P < 0.01). FGF-23 was associated with increased plaque % calcium-like tissue. Participants with no coronary artery disease had significantly lower phosphate levels. Phosphate was associated with higher grayscale median (GSM) in male subjects but with lower GSM in female subjects. FGF-23 was associated with increased plaque % fat in male subjects but increased plaque % calcium in female subjects.ConclusionsPhosphate was independently associated with the severity of atherosclerosis in terms of plaque burden and composition. FGF-23 was associated with plaque calcification. These findings suggest that abnormal phosphate homeostasis may play an under-recognized but potentially modifiable role in cardiovascular disease.

Serum biomarkers for arterial calcification in humans: A systematic review

“…However, these results were not adjusted for possible confounders ( Xiao et al, 2013 ). The other three studies that found a positive association included smaller study populations, ranging from 148 to 204 participants, and lower quality of evidence ( Masai et al, 2013 ; Holden et al, 2018 ; Morita et al, 2015 ). The papers that reported no significant associations were of moderate quality of evidence and included smaller study populations, ranging from 30 to 325 included participants ( Cancela et al, 2012 ; Razavi et al, 2021 ; Martín-Reys et al, 2016 ; Roos et al, 2008 ; Zamparini et al, 2018 ).…”

“…Five of ten included studies that analyzed a possible association between FGF-23 and arterial calcification showed a positive association ( Masai et al, 2013 ; Holden et al, 2018 ; Kestenbaum et al, 2014 ; Xiao et al, 2013 ; Morita et al, 2015 ). The other five showed no significant association ( Cancela et al, 2012 ; Razavi et al, 2021 ; Martín-Reys et al, 2016 ; Roos et al, 2008 ; Zamparini et al, 2018 ).…”

The Multifunctional Contribution of FGF Signaling to Cardiac Development, Homeostasis, Disease and Repair

“…Cohort studies on end-stage renal disease patients with severe cardiac complications indicated enhanced serum levels of FGF23 and calcium. FGF23 elevation is accompanied by an Falcini et al, 2013;Mathew et al, 2014;Chua et al, 2019;Holden et al, 2019 Causative Chronic kidney diseaseassociated cardiac complications…”

“…FGF23 is elevated in CAD patients with a history of type 2 diabetes or a high risk of atherosclerosis ( Lutsey et al, 2014 ; Tuñón et al, 2016 ; Holden et al, 2019 ). FGF23 is involved in atherosclerosis-related damage through advanced vascular plaque calcification ( Holden et al, 2019 ).…”

“…FGF23 is elevated in CAD patients with a history of type 2 diabetes or a high risk of atherosclerosis ( Lutsey et al, 2014 ; Tuñón et al, 2016 ; Holden et al, 2019 ). FGF23 is involved in atherosclerosis-related damage through advanced vascular plaque calcification ( Holden et al, 2019 ). FGF23 levels are increased in the serum of patients with Kawasaki syndrome, as another type of coronary artery abnormality which is associated with severe cardiovascular complications in children ( Falcini et al, 2013 ).…”