Calciotropic and phosphaturic hormones in heart failure

Abstract Aims Despite adherence to evidence-based guidelines, heart failure [HF] still results in 5-year mortality rates of 50%, indicating a need to implement additional preventive/intervention strategies. This review summarizes data on alterations in the calciotropic and phosphaturic hormones 1,25-dihydroxyvitamin D [1,25(OH) 2 D] and fibroblast growth factors-23 [FGF-23] in HF and discusses non-pharmacological measures for targeting these hormones. Data synthesis The role of 1,25(OH) 2 D in the regulation of calcium and phosphate homeostasis is central. 1,25(OH) 2 D also plays a pivotal role in cardiac function, but is downregulated by FGF-23. There is accumulating evidence from epidemiological data that HF is associated with decreased circulating 1,25(OH) 2 D and elevated FGF-23 levels. In patients with failing hearts, very low 1,25(OH) 2 D and extremely high FGF-23 levels have been reported. Experimental data support the assumption that vitamin D deficiency and high serum phosphate/FGF-23 levels increase the risk of HF. This review provides a hypothesis of how vitamin D deficiency, high calcium/phosphorus intake, physical inactivity, and age-related renal impairment may all contribute to HF by adversely affecting calcium- and phosphate-regulating hormones. Several case series in infants and a meta-analysis of randomized controlled trials in adults have already reported successful treatment of or a significant risk reduction in HF by vitamin D supplements. The association of calcium/phosphorus intake, physical activity, or renal function with calciotropic/phosphaturic hormones and HF is however less well documented. Conclusions More attention should be paid in future to the association of circulating 1,25(OH) 2 D and FGF-23 levels with HF and to (non-pharmacological) measures for targeting these calciotropic/phosphaturic hormones.