Circulating N‐Linked Glycoprotein Side‐Chain Biomarker, Rosuvastatin Therapy, and Incident Cardiovascular Disease: An Analysis From the JUPITER Trial

Abstract

Background GlycA, a novel protein glycan biomarker of N ‐acetyl side chains of acute‐phase proteins, was recently associated with incident cardiovascular disease ( CVD ) in healthy women. Whether GlycA predicts CVD events in the setting of statin therapy in men and women without CVD but with evidence of chronic inflammation is unknown. Methods and Results In the Justfication for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin ( JUPITER ) trial ( NCT 00239681), participants with low‐density lipoprotein cholesterol <130 mg/dL and high‐sensitivity C‐reactive protein (hs CRP ) ≥2 mg/L were randomized to rosuvastatin 20 mg/day or placebo. GlycA was quantified by nuclear magnetic resonance spectroscopy in 12 527 before randomization and 10 039 participants at 1 year. A total of 310 first primary CVD events occurred during maximum follow‐up of 5.0 years (median, 1.9). GlycA changed minimally after 1 year on study treatment: 6.8% and 4.7% decrease in the rosuvastatin and placebo groups, respectively. Overall, baseline GlycA levels were associated with increased risk of CVD : multivariable‐adjusted hazard ratio ( HR ) per SD increment, 1.20 (95% CI , 1.08–1.34; P =0.0006). After additionally adjusting for hs CRP , this was slightly attenuated (HR, 1.18; 95% CI , 1.04–1.35; P =0.01). On‐treatment GlycA levels were also associated with CVD ; corresponding multivariable‐adjusted HR s per SD before and after additionally adjusting for hs CRP : 1.27 (95% CI , 1.13–1.42; P <0.0001) and 1.24 (95% CI , 1.07–1.44; P =0.004), respectively. Tests for heterogeneity by treatment arm were not significant ( P for interaction, >0.20). Conclusion In the JUPITER trial, increased levels of GlycA were associated with an increased risk of CVD events independent of traditional risk factors and hs CRP . Clinical Trials Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00239681.