Elevated Serum Fibroblast Growth Factor 23 (FGF-23) Perseveres into a Convalescence Period After Elective Cardiac Surgery, with Receptor Activator of Nuclear Factor κB Ligand (RANKL) and Cartilage Oligomeric Matrix Protein (COMP) Being Part of the Peri-Surgical Pro-Arteriosclerotic Inflammatory Response

BACKGROUND: Receptor activator of nuclear factor κ B ligand (RANKL), osteoprotegerin (OPG), cartilage oligomeric matrix protein (COMP), bone morphogenetic protein (BMP-2), and fibroblast growth factor 23 (FGF-23) are involved in inflammation, calcium deposition, and fibrosis of blood vessels. Acute changes in these factors may contribute to the progression of arteriosclerosis, especially if their elevated serum levels persist postoperatively. MATERIAL/METHODS: A total of 90 patients (79 White, 4 African American, and 7 Other) undergoing elective heart surgery were enrolled in the study. Blood was collected before surgery and after surgery at 24 hours, 7 days, and 3 months to allow for longitudinal comparisons. After the plasma isolation, several biomarkers levels were studied using an enzymatic-linked assay. Demographic and clinical information were obtained from electronic health records. RESULTS: At 24 hours after surgery, RANKL (RANKL(baseline)=248.7±215.7 vs RANKL(t24h)=376.4±329.7; P=0.035), and BMP-2 (BMP-2(baseline)=283.7±255.4 vs BMP-2(t24h)=482.4; P=0.015) were significantly elevated compared to baseline, with levels returning to baseline at 7 days. FGF-23 increased significantly from baseline (FGF-23(baseline)=1020±1210) to 7 days (FGF-23(7d)=2191±5188; P=0.029) and remained significantly higher than baseline at 3 months (FGF-23(3m)=2041±3521; P=0.044). White blood cells (WBC) remained elevated at discharge (WBC(baseline)=6.8±2.1 vs WBC(24h)=15.0±5.3 vs WBC(discharge) =8.8±3.4). IL-8 and C-reactive protein normalized at 3 months. Estimated blood loss was significantly correlated with RANKL at 24 hours (r(2)=0.33; P=0.035). Serum creatinine levels after surgery at 24 hours (r(2)=0.41; p=0.008) and 7 days (r(2)=0.59; P=0.000) was strongly correlated with COMP. CONCLUSIONS: Persistent elevation of serum FGF-23 indicates a potential for accelerated arteriosclerosis after cardiac surgery.