Biomarkers of mineral metabolism and progression of aortic valve and mitral annular calcification: The Multi-Ethnic Study of Atherosclerosis

Background and aims: Previous research has implicated dysregulation of phosphate metabolism and calcium-phosphate solubilization in cardiovascular calcification, but epidemiologic studies evaluating longitudinal associations with valvular or annular calcification by computed tomography (CT), a highly sensitive imaging modality, are lacking. Our primary aim was to investigate the associations of mineral biomarkers with incidence and progression of aortic valve calcification (AVC)and mitral annular calcification (MAC). Methods: We evaluated the associations of serum FGF-23 (n = 6547 participants), phosphate (n = 6547), and fetuin-A (n = 2550)measured at baseline in the community-based Multi-Ethnic Study of Atherosclerosis with AVC and MAC on CT performed at baseline and at a median of 2.4 (1.6, 3.1)years later. We used linear mixed-effects models to account simultaneously for prevalence, incidence and progression of AVC and MAC. Results: After adjustment for demographic and clinical characteristics, a significant association was documented for FGF-23 with accelerated annual progression of MAC (2.83 Agatston units (AU), 95% CI = 0.49, 5.17 AU, per standard deviation (18.46 pg/mL)of FGF-23), but this was not seen for phosphate or fetuin-A. None of these biomarkers was associated with accelerated annual progression of AVC. Conclusions: This study provides evidence relating serum FGF-23 to accelerated annual MAC progression. Whether this mineral regulator is a risk marker or is involved in pathogenesis merits further investigation.