Method: HDL was isolated from 40 patients with RA and 40 age and sex matched healthy controls. Cholesterol efflux experiments were performed as described previously (Navab et al. Circulation 2004; 109(25):3215-3220). HDL’s anti-oxidant function was assessed by cell free assay as described previously (Charles-Schoeman et al. Arthritis Rheum 2009; 60(10):2870-2879), which assesses the ability of patient HDL to inhibit oxidation of a stock LDL. Lipoprotein cholesterol levels were determined by standard methods.
Result: Mean cholesterol efflux capacity of HDL was not significantly different between RA patients (40.2% ± 11.1%) and controls (39.5% ± 8.9%); p=0.75. However, HDL from RA patients with high disease activity measured by a disease activity score using 28 joint count (DAS28 > 5.1), had significantly decreased ability to promote cholesterol efflux compared to HDL from patients with low disease activity (DAS28 < 2.6). In addition, a significant correlation was noted between cholesterol efflux and disease activity measured by the DAS28 (r= -0.39, p=0.01). Higher RA disease activity was associated with decreased efflux by HDL. A similar correlation was observed with ESR, (r= -0.41, p=0.0009), and a trend noted with HS-CRP (r= -0.29, p=0.08). HDL’s ability to promote cholesterol efflux was modestly but significantly correlated with its anti-oxidant function (r = -0.34, p= 0.03).
Conclusion: Cholesterol efflux capacity of HDL is impaired in RA patients with high disease activity and is correlated with systemic inflammation and HDL’s anti-oxidant capacity. Attenuation of HDL function, independent of HDL cholesterol levels, may suggest a mechanism by which active RA contributes to increased CV risk.
Disclosure: C. Charles-Schoeman, None; Y. Y. Lee, None; V. Grijalva, None; J. D. FitzGerald, None; V. K. Ranganath, None; M. Taylor, None; M. A. McMahon, None; H. E. Paulus, None; S. T. Reddy, None.