Article Biomarkers of Vascular Calcification and Mortality in

Background Vascular calcification is common among patients undergoing dialysis and is associated with mortality. Factors such as osteoprotegerin (OPG), osteopontin (OPN), bonemorphogenic protein-7 (BMP-7), and fetuin-A are involved in vascular calcification. Design, setting, participants, &measurementsOPG, OPN, BMP-7, and fetuin-Aweremeasured in blood samples from 602 incident dialysis patients recruited fromUnited States dialysis centers between 1995 and 1998 as part of the Choices for HealthyOutcomes In Caring for ESRD Study. Their associationwith all-cause and cardiovascular mortality were assessed using Cox proportional hazards models adjusted for demographic characteristics, comorbidity, serum phosphate, and calcium. An interaction with diabetes was tested because of its known association with vascular calcification. Predictive accuracy of selected biomarkers was explored by C-statistics in nested models with training and validation subcohorts. Results Higher OPG and lower fetuin-A levels were associated with higher mortality over up to 13 years of follow-up (median, 3.4 years). The adjusted hazard ratios (HR) for highest versus lowest tertile were 1.49 (95 % confidence interval [95 % CI], 1.08 to 2.06) for OPG and 0.69 (95 % CI, 0.52 to 0.92) for fetuin-A. In stratified models, the highest tertile of OPG was associated with higher mortality among patients withou