Plasma Fibroblast Growth Factor 23, Parathyroid Hormone, 25-Hydroxyvitamin D3, and Risk of Heart Failure: A Prospective, Case-Cohort Study

Context: Bone mineral metabolism may play a role in the development of heart failure (HF). Objective: The aim of the study was to investigate the relationships of plasma fibroblast growth factor (FGF) 23, PTH, and 25-hydroxyvitamin D3 [25(OH)D3] with incident congestive HF in a population- based cohort of men and women aged 40-65 and 35-65 years, respectively, at baseline. Design: We conducted a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, including a randomly drawn sample of the total cohort free of HF and all incident HF cases that occurred during a mean follow-up of 8.2 +/- 1.6 years. Participants and Setting: A total of 221 incident congestive HF cases and 1228 individuals free of HF were included in the study. Main Outcome Measures: Incident congestive HF was measured. Results: In a multivariable model, each doubling of FGF23 [ie, per log (base 2) unit higher FGF23] was associated with a 29% higher HF risk (hazard ratio, 1.29 [95% confidence interval (CI), 1.07-1.56]). After multivariable adjustment, including estimated glomerular filtration rate, PTH was not related to HF risk (hazard ratio per doubling of PTH, 1.21 [95% CI, 0.99-1.48]). However, an interaction was observed between PTH and obesity, suggesting a relationship with HF risk in obese, but not in nonobese individuals. The hazard ratio for HF per doubling of 25(OH)D3 was 1.02 (95% CI, 0.73-1.41). Conclusions: Our findings provide epidemiological evidence for a positive relationship between FGF23 and risk of HF. The role of PTH in the development of HF remains unclear, in particular in obese individuals, until further confirmation in other studies. 25(OH) D3 was not related to HF.