Abstract 17731: Protein Glycan Side-Chains, Rosuvastatin Therapy, and Incident Vascular Events: An Analysis from the JUPITER Trial
Background: GlycA, a novel protein glycan biomarker of N-acetyl side-chains of acute-phase proteins, was recently shown to predict incident CVD in healthy women. The utility of GlycA for predicting future vascular events in the setting of statin therapy in men and women without CVD but with evidence of chronic inflammation is unknown
Methods: In JUPITER (NCT00239681), participants with LDL cholesterol <130 mg/dL and hsCRP≥2 were randomized to 20mg daily of rosuvastatin vs placebo. GlycA was quantified by NMR spectroscopy (LipoScience, NC) in 12 527 participants before and 1-year after randomization
Results: 310 first vascular events occurred during maximum follow-up of 5.0 (median, 2.0) years. Rosuvastatin lowered GlycA by 6.8% at 1 year while a 4.7% reduction was observed among those on placebo. Overall, baseline GlycA levels (median, 25th-75th percentile: 404, 364-449 μmol/L) were associated with increased risk of vascular events: multivariable adjusted HR per 1-SD increment in GlycA 1.20 (95% CI 1.08-1.34; p= 0.0006; Table). This association was attenuated but remained significant after additionally adjusting for hsCRP (HR per 1-SD: 1.18, 95% CI 1.04-1.35; p=0.01). On-treatment GlycA levels (median, interquartile range: 379, 341 to 423 μmol/L) were also significantly associated with vascular events; corresponding results were 1.27 (95% CI 1.13-1.42; p<0.0001) in multivariable adjusted model and 1.24 (95% CI 1.07-1.44; p=0.004) after additionally adjusting for hsCRP. Compared with placebo, the association of GlycA with vascular events in the rosuvastatin group was attenuated, although statistical tests for heterogeneity by treatment arm were not significant (p for interaction at baseline and 1-year were >0.20)
Conclusion: Among JUPITER participants recruited on the basis of an elevated hsCRP and low LDL cholesterol, elevated levels of GlycA were associated with an increased risk of vascular events independent of traditional clinical risk factors and hsCRP.
Author Disclosures: A.O. Akinkuolie: None. R.J. Glynn: Research Grant; Significant; Dr Glynn has received research support from AstraZeneca and NIH. P.M. Ridker: Research Grant; Significant; Novartis, AstraZeneca, Aegerion, ISIS, Boeringer, Pfizer, NHLBI, NCI. Other Research Support; Significant; Amgen.. Honoraria; Modest; Lilly, Genetech. Consultant/Advisory Board; Modest; ISIS, BostonHeart, Genzyme,Jannson. Other; Modest; Listed as a coinventor on patents held by BWH that relate to the use of inflammatory biomarkers to cardiovascular disease. S. Mora: Research Grant; Significant; AstraZeneca (AstraZeneca supported the original JUPITER study), Atherotech Diagnostics, NHLBI, LipoScience performed the GlycA assay at no additional cost. Consultant/Advisory Board; Modest; Quest Diagnostics,Cerenis Therapeutics, Lilly, Sanofi-Genzyme.
- © 2014 by American Heart Association, Inc.