Abstract P346: Novel Protein Glycan Derived Marker of Systemic Inflammation is Associated with Incident Coronary Heart Disease and Ischemic Stroke

Background: Enzymatically glycosylated proteins participate in multiple cellular processes, with variations in their concentration implicated in innate immunity and chronic inflammation. In addition, most inflammatory proteins are enzymatically glycosylated. GlycA is a novel nuclear magnetic resonance (NMR) biomarker whose signal originates from the N-acetyl groups of N-acetylglucosmine and N-acetylgalatosamine moieties of protein glycans. We assessed the association of GlycA with both incident CHD and ischemic stroke and performed a comparative analysis with hsCRP. Method: GlycA was quantified by proton NMR spectroscopy (LipoScience, NC) and hsCRP by immunoturbidimetric assay (Denka Seiken) in 27 649 participants of the Women’s Health Study. During a median follow up of 17 years, 1 089 incident cases of CHD and 465 incident cases of ischemic stroke were confirmed. Results: GlycA correlated with LDL cholesterol (r = 0.17), HDL cholesterol (r = -0.27), triglycerides (r = 0.47), BMI (r = 0.41) and hsCRP (r = 0.61), all p<0.0001. Multivariable-adjusted HRs (95% CIs) for top versus bottom quartiles of GlycA were 1.78 (1.44-2.20) with CHD and 1.50 (1.11-2.03) with ischemic stroke respectively (p-trend for both ≤ 0.006); these associations were similar in magnitude to that obtained for hsCRP and were weakened but remained significant after adjustment for lipids. (Table) Further adjustment for hsCRP attenuated the associations which were no longer statistically significant (p-trend ≥0.40 for both CHD and ischemic stroke). Conclusion: A novel protein glycan derived biomarker, GlycA, was associated with a graded increase in the risk of both incident CHD and ischemic stroke in this prospective study of initially healthy women in a manner similar to hsCRP. Adjustment for hsCRP attenuated this association, consistent with a possible role for protein glycans in inflammation.