Serum free 25(OH)D concentrations and cardiovascular disease, heart failure, kidney function decline, and fracture: the health, aging, and body composition study.

Vitamin D deficiency is common across the world. However, the standard clinical biomarker for vitamin D, 25OHD, may be a poor marker of vitamin D status, as most of circulating vitamin D is protein bound and not bioavailable. Free (unbound) vitamin D may therefore be a better marker of vitamin D status. We evaluated the relationship of free vitamin D with incident cardiovascular disease (CVD), heart failure (HF), kidney function decline (KFD) and fracture, among 786 participants in the Health Aging and body composition study. We used sequential models to assess hazard ratios (HRs) of each outcome that adjusted for age, sex, race, season of blood sampling, and study site, kidney function, serum calcium and phosphate, FGF 23, PTH, BMI, and vitamin D supplementation. The mean age of the 786 participants was 75 ± 3 yr, 53% were women, and 40% were Black. The median free vitamin D concentration was 5.3 (interquartile range 4.1-6.7) pg/mL. There were 157 cases of incident CVD, 123 cases of incident HF, 382 cases of incident KFD, and 178 fractures over 11 yr of follow-up. In fully adjusted models, a 2-fold greater free vitamin D was associated with lower risk of incident HF [HR 0.75, 95%CI,0.58-0.96 ] and greater risk KFD [1.25(1.03-1.52)]. We found no association between free vitamin D and incident CVD or fracture. We did not find evidence that free vitamin D was a superior marker of clinical outcomes compared to total 25OHD alone. Further studies are needed to elucidate the relationship of free vitamin D with clinical outcomes.