Background Patients with active rheumatoid arthritis (RA) are frequently diagnosed with an atherogenic lipid profile and supra-aortic vessel ultrasound signs of atheromatous plaques, which have been linked to the inflammatory activity of RA. Recent experimental and clinical evidences suggest that the beneficial effects of statins are pleiotropic and have been proposed to have anti-inflammatory and immunomodulatory effects, inhibiting proinflammatory cytokines (IL-1β, 6, 8, TNF-α), adhesion molecules (sICAM 1, E-, P-selectin), osteoprotegerin, which are implicated in RA pathogenesis. However, the beneficial role of statin therapy in clinical improvement and their benefit-risk profile are still debatable.
Objectives To evaluate the effect of medium-term rosuvastatin therapy on lipid profile, endothelial dysfunction and RA activity in patients with rheumatoid arthritis (RA) in comparison with conventional disease modifying antirheumatic drugs (DMARD) therapy.
Methods The study included 82 patients in the Specialized Course Out-patient Therapy Department of the 1st Clinic of Tashkent Medical Academy of age group between 44 and 65 years (mean 52±8.4), predominantly female gender (n=57, 69.5%), with early RA (mean disease duration 9.2±2.4 months), and divided into 2 groups. Group 1 (n=40) received methotrexate (MTX; 7.5 mg/week; plus prednisolone (10 mg/day). Group 2 (n=42) received MTX and prednisolone with the same previous doses plus rosuvastatin (40 mg/day). Lipid profile assessment comprised triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C). Disease activity was assessed by the disease activity score of 28 joints (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and visual analog scale (VAS). Disease activity, lipid profile and intima-media thickness (IMT) of common carotid arteries were measured before and after 85 days (6 months) of treatment.
Results 4 patients receiving rosuvastatin were excluded due to abnormal liver function test parameters (De Ritis ratio <0.9), further assessment was thus performed on 78 (Group 2, n=38) early RA patients. Overall ESR (Group 1: 24.4±7.26; Group 2: 37.4±12.3) and CRP (Group 1: 5.56±0.58; Group 2: 3.71±1.23) declined significantly during the treatment. The mean DAS28, unconditionally considered as the most important index of clinical disease activity in RA, was found to be lower (p<0.05) in the adjunct statin-treated group (Group 2: 3.68±0.77) than that of the conventional DMARD treated group (Group 1: 4.45±1.08). Statin significantly reduced LDL-C (3.9±1.2 mmol/l to 3.3±0.8 mmol/l; p=0.08) and increased HDL-C (1.3±0.6 mmol/l to 2.0±0.4 mmol/l; p=0.06) after 6 months of treatment. However, rosuvastatin therapy showed no significant improvement in VAS score (6.7±1.5 to 6.9±0.6; p=0.41) and IMT (1.04±0.09 to 1.08±0.07; p=0.05).
Conclusions Statins ameliorate RA activity, reduce potential cardiovascular risk in the context of atherosclerosis and mediate clinically apparent anti-inflammatory effects, but long-term effects and benefit-risk profile should be addressed in the management of elevated risk of cardiovascular events in RA patients.
Husain K., Hernandez W., Ansari R. A., Ferder L. Inflammation, oxidative stress and renin angiotensin system in atherosclerosis. World Journal of Biological Chemistry. 2015;6(3):209–217.
Disclosure of Interest None declared