Abstract: Effects of High-dose Atorvastatin on Antiinflammatory Properties of High Density Lipoprotein in Patients with Rheumatoid Arthritis: A Pilot Study

Effects of High-dose Atorvastatin on Antiinflammatory Properties of High Density Lipoprotein in Patients with Rheumatoid Arthritis: A Pilot Study

CHRISTINA CHARLES-SCHOEMAN, DINESH KHANNA, DANIEL E. FURST, MAUREEN McMAHON, SRINIVASA T. REDDY, ALAN M. FOGELMAN, HAROLD E. PAULUS, GRACE S. PARK, TIMOTHY GONG, and BENJAMIN J. ANSELL

ABSTRACT.

Objective. Patients with rheumatoid arthritis (RA) have a 2–3-fold increased risk of myocardial infarction. Recent work suggests that plasma high density lipoproteins (HDL) from patients with RA are more proinflammatory than HDL from controls. We examined the effects of atorvastatin 80 mg daily on the inflammatory properties of HDL and clinical disease activity in RA.

Methods. Twenty subjects with active RA (mean Disease Activity Score 5.13 ± 0.92) without dyslipidemia and no history of coronary artery disease were randomized in a double-blind placebo-controlled trial to receive 80 mg of atorvastatin (A) or placebo (P) daily in addition to stable antirheumatic drug therapy. Disease activity variables were followed over 12 weeks and the anti-/proinflammatory properties of HDL were determined by a cell-free assay (CFA) that measures lipid oxidation products.

Results. After 12 weeks, subjects completing the A protocol had a mean reduction in CFA values of 14.8 ± 21.7%, while subjects completing P protocol had a mean increase in CFA values of 7.1 ± 13.2% (p = 0.026). There was a trend for a decrease in highly sensitive C-reactive protein (hs-CRP) over 12 weeks in the A group compared to an increase in hs-CRP in the P group (p > 0.05), but changes in measures of clinical disease activity and plasma cytokine/intercellular adhesion molecule-1 levels were not significantly different in the A and P groups.

Conclusion. In patients with active RA, HDL was rendered more antiinflammatory by high-dose atorvastatin compared to placebo. Functional characterization of HDL may warrant further investigation as a method of cardiovascular risk assessment in RA patients without traditional coronary risk factors. (ClinicalTrials.gov number NCT00356473). (First Release June 1 2007; J Rheumatol 2007;34:1459-64)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
ATHEROSCLEROSIS
INFLAMMATION

From the Division of Rheumatology, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, California, USA.

Supported in part by grant HL-30568 and the Laubisch, Castera, Corday, and M.K. Grey Funds at UCLA. Atorvastatin was provided by Pfizer. Drs. Reddy and Fogelman are principals in Bruin Pharma; Dr. Fogelman is an officer in Bruin Pharma; and Dr. Ansell is a stockholder in Bruin Pharma.

C. Charles-Schoeman, MD; D.E. Furst, MD; M. McMahon, MD, MS; H.E. Paulus, MD; G.S. Park, MPH, Division of Rheumatology; S.T. Reddy, PhD; A.M. Fogelman, MD; T. Gong, BA; B.J. Ansell, MD, Division of Cardiology, Atherosclerosis Research Unit, UCLA David Geffen School of Medicine; D. Khanna, MD, MS, Division of Immunology, University of Cincinnati, Cincinnati, Ohio, USA.

Address reprint requests to Dr. C. Charles-Schoeman, David Geffen School of Medicine at UCLA, 1000 Veteran Avenue, 32-59 Rehab, Box 951670, Los Angeles, CA 90095-1670. E-mail: ccharles@mednet.ucla.edu

Accepted for publication March 5, 2007.