764 - Cholesterol Efflux by High Density Lipoproteins Is Impaired in Patients with Active Rheumatoid Arthritis

Sunday, November 6, 2011: 3:45 PM
W375a (McCormick Place West)
Christina Charles-Schoeman1, Yuen Yin Lee2, Victor Grijalva3, John D. FitzGerald2, Veena K. Ranganath4, Mihaela Taylor2, Maureen A. McMahon2, Harold E. Paulus4 and Srinivasa T. Reddy3, 1UCLA David Geffen School of Medicine, Los Angeles, CA, 2UCLA, Los Angeles, CA, 3UCLA, Los Angeles, 4University of California, Los Angeles, Los Angeles, CA
Presentation Number: 764

Background/Purpose: Reverse cholesterol transport (RCT) and prevention of oxidative stress are two major anti-atherogenic functions of high density lipoprotein (HDL). We previously showed that the anti-oxidant function of HDL in patients with rheumatoid arthritis (RA) is abnormal and associated with high levels of systemic inflammation. Since inflammation has been proposed to impair RCT, in the current work, we evaluated whether the RCT capacity of HDL from RA patients is impaired when compared to healthy controls.

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.

Keywords: atherosclerosis, cholesterol and rheumatoid arthritis (RA)

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.