Background: GlycA, a composite biomarker of systemic inflammation, predicts cardiovascular morbidity and mortality. Despite growing evidence regarding the association of GlycA and CVD, there are no data about the association of GlycA with coronary artery calcium (CAC), a marker of subclinical atherosclerosis. Objective: To investigate the relationship between GlycA levels and progression of CAC. Methods: MESA is a multiethnic cohort study of 6814 men and women aged 45-84 years, free of clinical CVD at baseline. Serum level of GlycA was measured by nuclear magnetic resonance (NMR) spectroscopy at baseline. CAC score was assessed by CT at baseline and follow up using either a cardiac gated electron beam CT scanner or 4-16 detector CT systems. Progression of CAC from baseline was defined as average yearly change in Agatston score >= 3 for CAC 0 to 100 and >=10% for CAC >100. Mean follow up period was 9.6±0.6 years. Multivariate regression analysis was performed adjusting for atherosclerotic risk factors. Results: Cross-sectional mean GlycA level, stratified by race/ethnicity, was higher in those with CAC > 0 compared to no CAC across all race/ethnicity groups and in both men and women (Fig1A). In regression analysis, the progression of annualized CAC was associated with higher baseline GlycA levels (Fig1B). Analysis was stratified due to interaction between GlycA and BMI (Fig2). In multivariable adjusted models, a one unit increase in GlycA was related to 0.23% higher average annual CAC change in normal BMI (p=0.002). In those who were excess weight (BMI >25) one unit increase in GlycA was associated with a 0.04% yearly average CAC change, after adjusting for covariates(p=0.07). Conclusion: Participants with higher baseline GlycA levels have CAC >0 as compared to lower baseline GlycA levels. The annualized progression of CAC is also higher in participants with baseline elevated GlycA levels. This association was statistically significant in participants with normal BMI.