Cholesterol efflux by high density lipoproteins is impaired in patients with active rheumatoid arthritis

Abstract

Objectives Reverse cholesterol transport (RCT) is a major antiatherogenic function of high density lipoprotein (HDL). In the current work, the authors evaluated whether the RCT capacity of HDL from rheumatoid arthritis (RA) patients is impaired when compared to healthy controls. Methods HDL was isolated from 40 patients with RA and 40 age and sex matched healthy controls. Assays of cholesterol efflux, HDL’s antioxidant function and paraoxanase-1 (PON-1) activity were performed as described previously. Plasma myeloperoxidase (MPO) activity was assessed by a commercially available assay. Results 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 very low disease activity/clinical remission (DAS28<2.6). Significant correlations were noted between cholesterol efflux and the DAS28 (r=−0.39, p=0.01) and erythrocyte sedimentation rate, (r=−0.41, p=0.0009). Higher plasma MPO activity was associated with worse HDL function (r=0.41/p=0.009 (antioxidant capacity); r=0.35, p=0.03 (efflux)). HDL’s ability to promote cholesterol efflux was modestly but significantly correlated with its antioxidant function (r=−0.34, p=0.03). Conclusions The cholesterol efflux capacity of HDL is impaired in RA patients with high disease activity and is correlated with systemic inflammation and HDL’s antioxidant capacity. Attenuation of HDL function, independent of HDL cholesterol levels, may suggest a mechanism by which active RA contributes to increased cardiovascular (CV) risk.

Associations of Hydroxychloroquine Use With Lipid Profiles in Rheumatoid Arthritis: Pharmacologic Implications

“…In view of the reported lipid paradox in relation to RA disease activity, we evaluated the impact of validated RA disease activity measures on lipid profiles based on HCQ status (13,36). While HCQ nonusers had higher DAS28-3v scores, the associations of lower lipid values with HCQ use were independent of disease activity, particularly in an established disease cohort at less risk of lipid changes related to RA treatment (16).…”

“…Further complicating the relationship of RA disease and CVD are the associations of the systemic inflammatory responses in RA with lipid profiles. There are reportedly low levels of density-defined lipids in active disease, yet there are elevations in protein-related moieties (apolipoproteins B and C III) (10,11), aberrations in cholesterol processing, increases in proinflammatory lipid profiles (12)(13)(14), and, in early, treated RA, increases in atherogenic profiles (15). In addition, the traditional RA therapies, such as prednisone and nonsteroidal antiinflammatory drugs, increase CVD risk, while newer biologic agents, such as tofacitinib and tocilizumab, include the adverse effect of hyperlipidemia in up to 10% and 20% of patients, respectively (4,10,16).…”

Psoriasis: it's more than just the skin

“…The paper by Holzer et al demonstrates that a relatively mild chronic infl ammatory state can similarly result in dysfunctional HDL leading to decreased cholesterol effl ux from macrophages ( 12 ). A very recent paper examining the function of HDL from patients with rheumatoid arthritis reported that HDL from patients with severe rheumatoid arthritis (CRP 5.7 ± 8.7 mg/dl) also had a decreased ability to promote cholesterol effl ux from macrophages, whereas HDL from patients with mild rheumatoid arthritis had a normal capacity to support effl ux ( 17 ). There was an inverse correlation between markers of infl ammation (sedimentation rate and CRP) and the ability of HDL to promote cholesterol effl ux ( 17 ).…”

“…A very recent paper examining the function of HDL from patients with rheumatoid arthritis reported that HDL from patients with severe rheumatoid arthritis (CRP 5.7 ± 8.7 mg/dl) also had a decreased ability to promote cholesterol effl ux from macrophages, whereas HDL from patients with mild rheumatoid arthritis had a normal capacity to support effl ux ( 17 ). There was an inverse correlation between markers of infl ammation (sedimentation rate and CRP) and the ability of HDL to promote cholesterol effl ux ( 17 ). Thus, infl ammation, if of a sufficient magnitude, can lead to alterations in HDL resulting in a decreased ability to promote cholesterol effl ux from macrophages.…”

Platelet and red blood cell interactions and their role in rheumatoid arthritis

“…Lipid parameters (e.g. cholesterol levels) of sufferers are also distinctly altered and resistant to potential modification [8]. The inflammatory processes Abstract Cytokines, lymphocytes, platelets and several biomolecules have long been implicated in the pathology of rheumatoid arthritis (RA), and the influences of antibody production and tagging, and cytokine, chemokine and enzyme production at specific rheumatoid joints were thought to be exclusive to the advancement of disease parameters.…”