Person:

Mora, Samia

Background: Glycosylated proteins partake in multiple cellular processes including inflammation. We hypothesized that GlycA, a novel biomarker of protein glycan N‐acetyl groups, is related to incident cardiovascular disease (CVD), and we compared it with high‐sensitivity C‐reactive protein (hsCRP). Methods and Results: In 27 491 initially healthy women, baseline GlycA was quantified by nuclear magnetic resonance spectroscopy and hsCRP by an immunoturbidimetric assay. During median follow‐up of 17.2 years, 1648 incident CVD events occurred (myocardial infarction, ischemic stroke, coronary revascularization, and CVD death). GlycA and hsCRP were moderately correlated (Spearman r=0.61, P<0.0001). In Cox regression models that included age, ethnicity, smoking, blood pressure, medications, menopausal status, body mass index, and diabetes, hazard ratios for CVD across quartiles 1 to 4 of GlycA were 1.00, 1.10 (95% CI, 0.92 to 1.30), 1.34 (95% CI, 1.13 to 1.58), and 1.64 (95% CI, 1.39 to 1.93), similar to hsCRP, for which hazard ratios were 1.00, 1.18 (95% CI, 0.99 to 1.41), 1.35 (95% CI, 1.14 to 1.61), and 1.75 (95% CI, 1.47 to 2.09) (both Ptrend<0.0001). Associations were attenuated after additionally adjusting for lipids: the hazard ratio of quartile 4 versus 1 for GlycA was 1.23 (95% CI, 1.04 to 1.46; Ptrend=0.002) and for hsCRP was 1.44 (95% CI, 1.20 to 1.72; Ptrend<0.0001). Further adjustment for the other biomarker resulted in a hazard ratio of quartile 4 versus 1 for GlycA of 1.03 (95% CI, 0.85 to 1.24; Ptrend=0.41) and for hsCRP of 1.29 (95% CI, 1.06 to 1.56; Ptrend=0.001). Conclusions: In this prospective study of initially healthy women, baseline GlycA was associated with incident CVD, consistent with a possible role for protein glycans in inflammation and CVD. Clinical Trial Registration URL: http//clinicaltrials.gov/. Unique identifier NCT00000479.

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.