Nandkeolyar S, et al. - Researchers assessed the link between novel biomarkers and their association with coronary atherosclerosis and its progression—as measured by coronary artery calcium (CAC)—by analyzing data on CAC and several biomarkers available at baseline and 4-year follow-up in 1,207 study participants from the EISNER study, a prospective trial of patients without known atherosclerotic cardiovascular disease (ASCVD). Biomarkers were standardized and summed for a composite score. The square-root (CAC_SQRT) method and rapid (top decile) progression defined CAC progression. Using adjusted regression models, a final prediction model for baseline CAC and CAC progression was proposed. A baseline CAC > 0 was present in 621 participants, in whom 323 progressed by CAC_SQRT, and 121 rapidly progressed. In persons free of ASCVD at baseline, osteopontin allowed identification of progression of atherosclerosis. Osteopontin may have utility as a predictive tool to guide ASCVD prevention management.