title: Circulating N-Linked Glycoprotein Side-Chain Biomarker, Rosuvastatin Therapy, and Incident Cardiovascular Disease: An Analysis From the JUPITER Trial.
abstract: 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.
  
  
  
  In the Justfication for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial (NCT00239681), participants with low-density lipoprotein cholesterol <130 mg/dL and high-sensitivity C-reactive protein (hsCRP) ≥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 hsCRP, 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 HRs per SD before and after additionally adjusting for hsCRP: 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).
  
  
  
  In the JUPITER trial, increased levels of GlycA were associated with an increased risk of CVD events independent of traditional risk factors and hsCRP.
  
  
  
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.
authors.affiliation: Center for Lipid Metabolomics, Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Akintunde O
authors.initials: AO
authors.lastname: Akinkuolie
authors.affiliation: Center for Lipid Metabolomics, Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA Department of Biostatistics, Harvard School of Public Health, Boston, MA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Glynn
authors.affiliation: Center for Lipid Metabolomics, Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Latha
authors.initials: L
authors.lastname: Padmanabhan
authors.affiliation: Center for Lipid Metabolomics, Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.affiliation: Center for Lipid Metabolomics, Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA smora@partners.org.
authors.forename: Samia
authors.initials: S
authors.lastname: Mora
mesh_terms: D000117:Acetylglucosamine / Q000097:blood*; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012306:Risk; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D015415:Biomarkers; D000068718:Rosuvastatin Calcium; D002097:C-Reactive Protein; D000117:Acetylglucosamine
keywords: cardiovascular disease; epidemiology; glycoprotein; metabolomics; statin intervention