The heart and kidney: Abnormal phosphate homeostasis is associated with atherosclerosis

Abstract

Context: Phosphate 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 counterregulatory hormone that increases renal phosphate excretion to maintain normal levels. Objective: The purpose of the study was to determine the association of phosphate and FGF-23 to atherosclerosis. Design and Setting: A prospective cohort study (n = 204) of outpatients referred for coronary angiography over of a 1-year recruitment period at the Kingston General Hospital. Intervention: Blood was collected, and a focused carotid ultrasound was performed. Main Outcome Measure: Degree 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. Results: Carotid 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. Conclusions: Phosphate 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.