Abstract 15297: High-Density Lipoprotein Function Associates With GlycA, a Novel Inflammation Marker, but Does Not Explain the Association Between GlycA and Incident Cardiovascular Events

Background: High-density lipoproteins (HDL) exert anti-atherosclerotic effects via reverse cholesterol transport, yet this process is impaired in the setting of inflammation. GlycA, a novel integrated glycosylation marker of five acute phase reactants, is linked to CV events. We assessed the hypothesis that GlycA is associated with impaired HDL function measures and that the association between GlycA and incident CV events is partially explained by dysfunctional HDL. Methods: Baseline measurements of HDL cholesterol (HDL-C), HDL particle concentration (HDL-P), and cholesterol efflux capacity were obtained from the Dallas Heart Study, a multi-ethnic cohort of 2225 adults without CVD. GlycA was derived from NMR spectral features. The primary end point was first nonfatal MI, nonfatal stroke, coronary revascularization, or CV death over a median of 11.4 years (N=171). Results: Median age was 43 with 56% women and 47% blacks. The correlation between GlycA and hs-CRP was 0.54 (p\u3c0.0001). HDL-P, HDL-C, and cholesterol efflux were inversely associated with GlycA when adjusted for traditional risk factors, hs-CRP, and all HDL measures (standardized beta estimates: -0.10, -0.20, and -0.06, respectively; all p\u3c0.0002). In Cox proportional hazards models adjusted for risk factors, GlycA was directly associated with incident CV events (HR for Q4 vs. Q1: 2.25, 95% CI 1.33 to 3.82). Further adjustment for cholesterol efflux did not attenuate this association (HR for Q4 vs. Q1: 2.13, 95% CI 1.25 to 3.63), while cholesterol efflux remained inversely associated (HR for Q4 vs. Q1: 0.59, 95% CI 0.39 to 0.89) with the primary outcome (Figure). Conclusions: Worsening inflammation as reflected by higher GlycA levels is associated with lower HDL-C, HDL-P, and cholesterol efflux. Cholesterol efflux does not appear to mediate the association between GlycA and incident CV events. Further studies are warranted to investigate the impact of inflammation on HDL function and CV disease. Download figure Footnotes Author Disclosures: K.A. Riggs: None. P.H. Joshi: Consultant/Advisory Board; Modest; Regeneron. A. Khera: None. K. Singh: None. O. Akinmolayemi: None. C.R. Ayers: None. A. Rohatgi: Research Grant; Significant; Merck. Other Research Support; Modest; NIH, AHA. Consultant/Advisory Board; Modest; Merck, CSL Limited, HDL Diagnostics, Cleveland HeartLabs