Background Atherosclerosis is an inflammatory disease, and the major cause of cardiovascular disease (CVD) including stroke, myocardial infarction (MI) and claudication. In systemic lupus erytheatosus (SLE), the risk of CVD is raised as compared to healthy controls and a combination of traditional and non-traditional risk factors appear to account for this1. Even though it is possible that other factors related to thrombosis contribute more to CVD in SLE than in the general population, increased prevalence of atherosclerotic plaques is associated with CVD also in SLE1. This finding has been confirmed in several case-control studies 1-4.
Objectives We here determine the role of antibodies against oxidized cardiolipin and phosphatidylserine (anti-OxCL and anti-OxPS) in SLE.
Methods Patients with SLE (n=114) were compared with age- and sex-matched population-based controls (n=122). Common carotid intima-media thickness (IMT) and plaque occurrence were determined by B-mode ultrasound. Plaques were graded according to echogenicity and grouped as 1-4, with 1 being echoluscent, and considered most vulnerable. Antibodies were studied by ELISA.
Results Prevalence of low IgM anti-OxPS (but not anti-OxCL) levels (below 33rd percentile) was increased in SLE (p=0.037). SLE-patients with atherosclerotic plaques had lower IgM anti-OxCL (p=0.031) and anti-OxPS (0.0034) and after adjusting for other risk factors (age, hyperlipidemia, hypertension and glucose), low anti-OxPS remained significant (p=0.028). Vulnerable plaques (total, or left side) were more prevalent among SLE-patients with low IgM anti-OxCL and anti-OxPS IgM aCL when controlled for other factors (p<0.05). Low total IgM was independently associated with vulnerable plaque on left side (p<0.05), but not with other atherosclerosis measures. IgM anti-CL and anti-PS were higher among SLE-patients with CV; (cardiopulmonary disease) than among those with no history of CV (p<0.05). There were no associations between antibodies and other disease manifestations or -activity. anti-OxCL and anti-OxPS in contrast to anti-CL and anti-PS, were beta2-GPI-independent.
Conclusions Co-factor β2GPI-independentIgM anti-OxCL and anti-OxPS have atheroprotective properties in SLE, being negatively associated with prevalence of plaques and vulnerable plaques.
Svenungsson E, Jensen-Urstad K, Heimburger M, Silveira A, Hamsten A, de Faire U, Witztum JL, Frostegard J. Risk factors for cardiovascular disease in systemic lupus erythematosus. Circulation. 2001;104(16):1887-1893.
Doria A, Shoenfeld Y, Wu R, Gambari PF, Puato M, Ghirardello A, Gilburd B, Corbanese S, Patnaik M, Zampieri S, Peter JB, Favaretto E, Iaccarino L, Sherer Y, Todesco S, Pauletto P. Risk factors for subclinical atherosclerosis in a prospective cohort of patients with systemic lupus erythematosus. Ann Rheum Dis. 2003;62(11):1071-1077.
Frostegard J. SLE, atherosclerosis and cardiovascular disease. J Intern Med. 2005;257(6):485-495.
Roman MJ, Shanker BA, Davis A, Lockshin MD, Sammaritano L, Simantov R, Crow MK, Schwartz JE, Paget SA, Devereux RB, Salmon JE. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med. 2003;349(25):2399-2406.
Disclosure of Interest J. Frostegård Shareholder of: Named as inventor on Patent applications, J. Su: None Declared, A. Frostegård: None Declared, X. Hua: None Declared, T. Gustafsson: None Declared, T. Jogestrand: None Declared, I. Hafström: None Declared