Effects of high-dose atorvastatin on antiinflammatory properties of high density lipoprotein in patients with rheumatoid arthritis: a pilot study.
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.


CONCLUSIONS
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).
Charles-Schoeman
Christina
C
Division of Rheumatology, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, California 90095-1670, USA. ccharles@mednet.ucla.edu
Khanna
Dinesh
D
Furst
Daniel E
DE
McMahon
Maureen
M
Reddy
Srinivasa T
ST
Fogelman
Alan M
AM
Paulus
Harold E
HE
Park
Grace S
GS
Gong
Timothy
T
Ansell
Benjamin J
BJ
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D000069059:Atorvastatin; D004305:Dose-Response Relationship, Drug; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D008075:Lipoproteins, HDL / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011758:Pyrroles / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D008075:Lipoproteins, HDL; D011758:Pyrroles; D000069059:Atorvastatin