Abstract 18909: Interaction Between a Novel Protein Glycan Derived Inflammation Biomarker (GlycA) and HDL Particle Subclasses on Mortality in a Cardiac Catheterization Cohort
Background: GlycA, a novel serum inflammatory biomarker composed of enzymatically glycosylated acute phase proteins, is associated with cardiovascular events in a primary prevention population. Emerging data suggest that inflammation may adversely impact HDL function. We sought to define the role of GlycA as a biomarker of adverse events in a secondary prevention population and to understand potential interactions between GlycA and HDL subclasses.
Methods: GlycA and medium and small HDL particles (MS-HDL) were measured with NMR spectroscopy in 7,617 individuals in the CATHGEN biorepository. Cox proportional hazards modeling was used to test the relationship of GlycA, MS-HDL and the GlycA*MS-HDL interaction term with time-to-death in multivariable models adjusted for 11 CV risk factors and stratified by diabetes status. We then assessed the ability of GlycA, MS-HDL, and GlycA*MS-HDL to improve risk discrimination in clinical models.
Results: Over a mean time-to-event of 2547 days, 2318 individuals died. Higher GlycA levels were associated with increased risk of death (HR 1.34 [1.29-1.39], p<0.0001). In diabetes-stratified models, the greatest quartile of GlycA in patients without diabetes conferred greater risk of mortality than the lowest quartile of GlycA in patients with diabetes. In models containing MS-HDL (main effect HR 0.69 [0.66-0.72], p<0.0001), addition of GlycA (HR 1.28 [1.24-1.32], p<0.0001) and GlycA*MS-HDL (p<0.0001) demonstrated independent associations of these variables with mortality. MS-HDL levels were associated with lower mortality risk at lower GlycA levels but with increased mortality risk at greater GlycA levels. There was an increasing improvement of model fit characteristics with incremental addition of GlycA, MS-HDL and GlycA*MS-HDL to robust clinical models.
Conclusion: GlycA is associated with an increased risk of mortality in a secondary prevention population. The interaction of GlycA with MS-HDL suggests that greater systemic inflammation can modify the association of HDL subclasses with clinical outcomes and at the highest levels of GlycA, may reverse the protective effect of HDL. These findings have implications for the interpretation of diagnostic and therapeutic tools involving HDL measurements.
Author Disclosures: R.W. McGarrah: None. D. Craig: None. C. Haynes: None. Z. Dowdy: None. S.H. Shah: None. W.E. Kraus: None.
- © 2015 by American Heart Association, Inc.