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

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 counter-regulatory 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.

Circulating Gas6 is associated with reduced human carotid atherosclerotic plaque burden in high risk cardiac patients.

OBJECTIVE: Pre-clinical studies suggest that growth arrest-specific protein 6 (Gas6), a member of the vitamin K dependent family of proteins, is implicated in atherosclerosis. A role for Gas6 in stabilizing atherosclerotic plaque has been suggested. Our aim was to determine the association between Gas6 and measures of carotid artery atherosclerosis in humans undergoing elective coronary angiography. Secondary aims were to determine the association between Gas6 and sex, diabetes, and obesity. METHODS: In 204 outpatients referred for coronary angiography, EDTA plasma was collected and a focused carotid ultrasound performed. Degree of angiographic coronary artery disease was scored. Carotid intima media thickness as well as maximum plaque height, plaque area, and grayscale median were measured by vascular sonography. Gas6 was assessed by enzyme-linked immunosorbent assay. RESULTS: We found that Gas6 concentrations were lower in males and were associated with diabetes, obesity, and lower kidney function. After adjustment for age, sex, kidney function, BMI and traditional cardiac risk factors; diabetes was associated with higher levels of Gas6, whilst there was a significant inverse relationship between Gas6 and total plaque area. Gas6 was inversely associated with maximum plaque height and total plaque area in adjusted multi-variable models. CONCLUSIONS: We observed higher levels of Gas6 in participantswith adverse cardiovascular risk profiles (e.g. diabetes, obesity) yet Gas6 was independently associated with reduced plaque height and total plaque area. These findings suggest that Gas6 may play a role in human atherosclerotic plaque remodeling.