FGF23 and Immune Activation are Correlated in Chronic Heart Failure and Additive Predictors of Poor Prognosis

Abstract

Aims: Immune activation and disturbances of vitamin D metabolism are frequently encountered in patients with heart failure. Elevated fibroblast growth factor 23 (FGF23) levels as well as immune activation have been associated with a worse outcome in patients with heart failure. We evaluated the relationship of vitamin D metabolism and FGF23 levels with immune activation and its association with cardiac function and outcome in patients with heart failure. Methods and Results: In 149 patients with heart failure caused by nonischaemic cardiomyopathy, parameters of vitamin D metabolism (vitamin D, parathormone, phosphate, C-terminal FGF23, calcium), inflammation (hsCRP, neopterin) and cardiac function were investigated. Patients with elevated inflammatory parameters had significantly higher Ct-FGF23 levels (37.33 RU/mL vs. 17.60 RU/mL, p < 0.001). The highest Ct-FGF23 and phosphate levels were found in patients with elevated neopterin and hsCRP levels as well as in in patients with progressive heart failure. Patients with high Ct-FGF23 and neopterin levels (Ct-FGF23 > 22.60 RU/mL, neopterin > 6.90 nmol/L) had a significantly higher risk for adverse events compared to patients with low Ct-FGF23 and neopterin levels (HR 7.386, [95%CI 2.543 – 21.447], p < 0.001). Conclusions: Our study indicates a strong relationship of vitamin D metabolism, especially FGF23, with Th1 immune activation in patients with heart failure. Elevated Ct-FGF23 and neopterin levels are additive predictors for adverse cardiovascular events in patients with heart failure.

Physiology and Inflammation Driven Pathophysiology of Iron Homeostasis—Mechanistic Insights into Anemia of Inflammation and Its Treatment

“…FGF23 further reduces the secretion of EPO and directly enhances erythrocyte apoptosis [266]. This may negatively affect AI pathogenesis, along with an effect of FGF23 on immune activation and a subsequent increased of hepcidin production [266][267][268][269][270][271].…”

“…First of all, cytokines not only suppress EPO production, they also suppress EPO-mediated signaling [174] and directly impair erythroid cell proliferation and differentiation [180]. Moreover, EPOR expression is inhibited by FGF23 [268], which is elevated in patients with an activated immune system [267,[278][279][280], hyperparathyroidism [281] or hyperphosphatemia [282]. Importantly, ID also negatively impacts on EPO signaling in erythroid cells via its effect on Scribble expression [98], but also blunts erythroid differentiation at later stages [283].…”