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

Robinson-Cohen C, Zelnick LR, Hoofnagle AN, Lutsey PL, Burke G, Michos ED, Shea SJC, Tracy R, Siscovick DS, Psaty B, Kestenbaum B, de Boer IH
J Clin Endocrinol Metab. 2017 102 (8): 3075-3084

PMID: 28472285 · PMCID: PMC5546864 · DOI:10.1210/jc.2017-00296

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.

Copyright © 2017 Endocrine Society

MeSH Terms (20)

African Americans Aged Aged, 80 and over Asian Continental Ancestry Group Biological Availability Case-Control Studies Coronary Disease European Continental Ancestry Group Female Hispanic Americans Humans Male Mass Spectrometry Middle Aged Proportional Hazards Models Protein Isoforms Risk Factors United States Vitamin D Vitamin D-Binding Protein

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