Utility of a novel inflammatory marker, GlycA, for assessment of rheumatoid arthritis disease activity and coronary atherosclerosis

Abstract

Introduction: GlycA is a novel inflammatory biomarker measured using nuclear magnetic resonance (NMR). Its NMR signal primarily represents glycosylated acute phase proteins. GlycA was associated with inflammation and development of cardiovascular disease in initially healthy women. We hypothesized that GlycA is a biomarker of disease activity and is associated with coronary artery atherosclerosis in patients with rheumatoid arthritis (RA).

Methods: We conducted a cross-sectional study of 166 patients with RA and 90 control subjects. GlycA was measured from an NMR signal originating from N-acetylglucosamine residues on circulating glycoproteins. The relationship between GlycA and RA disease activity (Disease Activity Score based on 28 joints (DAS28)) and coronary artery calcium score was determined.

Results: GlycA concentrations were higher in patients with RA (median (interquartile range): 398 μmol/L (348 to 473 μmol/L)) than control subjects (344 μmol/L (314 to 403 μmol/L) (P < 0.001). In RA, GlycA was strongly correlated with DAS28 based on erythrocyte sedimentation rate (DAS28-ESR) and DAS28 based on C-reactive protein (DAS28-CRP) and their components, including tender and swollen joint counts, global health score, ESR and CRP (all P < 0.001). The area under the receiver operating characteristic curve for GlycA's ability to differentiate between patients with low versus moderate to high disease activity based on DAS28-CRP was 0.75 (95% confidence interval (CI): 0.68, 0.83). For each quartile increase in GlycA, the odds of having coronary artery calcium increased by 48% (95% CI: 4%, 111%), independent of age, race and sex (P = 0.03).

Conclusion: GlycA is a novel inflammatory marker that may be useful for assessment of disease activity and is associated with coronary artery atherosclerosis in patients with RA.

Fig. 1

GlycA is higher in patients with rheumatoid arthritis compared with control subjects. Boxes represent the median (middle horizontal line) and the 25th and 75th percentiles. Whiskers represent the 5th and 95th percentiles. Each data point is presented as an open circle. Patients with rheumatoid arthritis had a higher GlycA concentration (median (interquartile range): 398 μmol/L (348 to 473 μmol/L)) compared with control subjects (344 μmol/L (314 to 403 μmol/L); P < 0.001)

Fig. 2

GlycA increases with increasing rheumatoid arthritis disease activity. Boxes represent the median (middle horizontal line) and the 25th and 75th percentiles. Whiskers represent the 5th and 95th percentiles. Each data point is presented as an open circle. Rheumatoid arthritis (RA) disease activity on the basis of Disease Activity Score based on 28 joints using erythrocyte sedimentation rate (DAS28-ESR) was defined as follows: remission = DAS28 < 2.6 (n = 39); low = DAS28 between 2.6 and 3.2 (n = 25); moderate = DAS28 between 3.2 and 5.1 (n = 67); and high = DAS28 > 5.1 (n = 33)