Objective. The effect of statins on atherogenesis in systemic lupus erythematosus (SLE) is poorly known. To inform a wider trial we performed a pilot study evaluating the intima-media thickness of the common carotid artery (CIMT) and some oxidative [beta-2-glycoprotein-1 complexed with oxidised low density lipoprotein ( 2GPIoxLDL)], metabolic [paraoxonase (PON), nitrate ( ), nitrite ( ) and nitrotyrosine (NT)], inflammatory [C-reactive protein (CRP) and serum amyloid A (SAA)], and lipid markers before and after 1 year of treatment with 40？mg of oral atorvastatin (AT). Methods. Randomised, double blind, placebo controlled pilot study on consecutive SLE patients: 17 SLE patients were randomised into the AT arm and 20 into the placebo arm. CIMT was measured by high-resolution sonography, PONa by a spectrophotometric method, and by a colorimetric assay and oxLDL- 2GPI, NT, CRP, and SAA by Elisa. Results. After correction for age and disease duration oxLDL- 2GPI decreased by 27% ( ) and PON/HDL ratio increased by 12% ( ) but CIMT did not change. Conclusion. This pilot study revealed a decrease of oxLDL- 2GPI (oxidant marker) and an increase of PON/HDL ratio (antioxidant activity) after AT indicating a favourable effect of the drug on atherogenic pathways that should be explored on larger trials. 1. Introduction Coronary artery disease (CAD) accounts for significant morbidity and mortality in patients with systemic lupus erythematosus (SLE) [1] being 8-fold more common than in the normal population after correction for the traditional Framingham risk factors [2]. First myocardial infarction occurs almost 20 years earlier than in the general population [3] with 90% of SLE women deceased between 16 to 37 years of age having severe atherosclerosis with greater than 75% occlusion in at least one coronary artery [4]. CAD explains the second curve of the bimodal mortality pattern in SLE, with early deaths attributed to the disease itself [5]. Because of the longer life expectancy of SLE early intervention is paramount to decrease the risk of vascular related death. Using high-resolution carotid ultrasound investigators have detected greater intima-media thickness of carotid arteries (CIMT) [6] and/or a greater frequency of carotid plaques in patients with SLE [7, 8] independently related to CAD [8]. Natural statins reduce cardiovascular risk and atherosclerosis progression [9] whereas synthetic statins such as atorvastatin (AT) induced a significant regression of CIMT in familial hypercholesterolaemia [10]. Accordingly we started a one-year placebo controlled pilot
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