Associations of Vitamin D-Binding Globulin and Bioavailable Vitamin D Concentrations With Coronary Heart Disease Events: The Multi-Ethnic Study of Atherosclerosis (MESA)

Context: Low 25-hydroxyvitamin D [25(OH) D] is associated with coronary heart disease (CHD) in people who are white and Chinese but not black or Hispanic. Vitamin D binding globulin (VDBG) avidly binds 25(OH) D, reducing its bioavailability, and differs in isoform and concentration by race. Objective: Evaluate associations of VDBG with CHD and whether accounting for VDBG or estimating bioavailable 25(OH) D explains the heterogeneity of the association of 25(OH) D with CHD. Design and Setting: We conducted a case-cohort study within the Multi-Ethnic Study of Atherosclerosis. Participants with an incident CHD event over 12 years of follow-up (n = 538) and a randomly assigned subcohort (n = 999) were included. We measured baseline 25(OH) D, VDBG, and isoforms using mass spectrometry and estimated bioavailable 25(OH) D from published equations. Results: VDBG was associated with an increased risk of CHD [hazard ratio, 1.77 (95% confidence interval, 1.46 to 2.14) per standard deviation increment, P < 0.0001], without evidence of heterogeneity by race or isoform (each P for interaction > 0.1). Low total 25(OH) D was differentially associated with CHD events, by race, with or without adjustment for VDBG (P for interaction = 0.04 or 0.05, respectively). Associations of 25(OH) D with CHD were strengthened with adjustment for VDBG among participants who were white or Chinese, and bioavailable 25(OH) D was associated with CHD events only among white participants. Conclusions: High VDBG concentration was associated with CHD events in all racial and ethnic groups. Incorporation of VDBG strengthened existing associations of 25( OH) D with CHD but did not explain racial heterogeneity in associations of 25( OH) D with CHD.