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 (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).

CONCLUSION:

In the JUPITER trial, increased levels of GlycA were associated with an increased risk of CVD events independent of traditional risk factors and hsCRP.

CLINICAL TRIALS REGISTRATION:

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

• Authors: Akintunde O Akinkuolie, Robert J Glynn, Latha Padmanabhan, Paul M Ridker, Samia Mora
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 5 Issue 7 (07 13 2016) ISSN: 2047-9980 [Electronic] England
• PMID: 27413042 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Chemical References

• Anticholesteremic Agents
• Biomarkers
• Rosuvastatin Calcium
• C-Reactive Protein
• Acetylglucosamine

Topics

• Acetylglucosamine (blood)
• Aged
• Anticholesteremic Agents (therapeutic use)
• Biomarkers (blood)
• C-Reactive Protein (analysis)
• Cardiovascular Diseases (blood, diagnosis, prevention & control)
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Risk
• Rosuvastatin Calcium (therapeutic use)