ABSTRACT
Traditional risk factors failed to fully account for the premature and accelerated development of atherosclerosis in systemic lupus erythematosus [SLE] patients. The low density lipoprotein [LDL] modification into oxidized LDL [ox-LDL] is a central event in atherogenesis that leads to a cycle of inflammation, endothelial dysfunction and atherosclerotic plaque formation. It is proposed that ox-LDL contributes to the development of autoimmune-mediated atherosclerosis. The metabolic syndrome is closely associated with subsequent development of type 2 diabetes mellitus and cardiovascular disease and is found to be highly prevalent in SLE patients. The aim of the present study was to investigate whether anti-oxLDL antibody [ox-LDL Ab] levels are altered in SLE patients and whether these alterations are related to insulin resistance, atherosclerosis, and components of the metabolic syndrome. Correlation with clinical and laboratory manifestations as well as SLE Disease Activity Index [SLEDAI] and Systemic Lupus International Collaborating Clinics [SLICC]/American College of Rheumatology Damage Index [SLICC/ACR DI] were studied. Thirty SLE women with a mean age of 27.63 +/- 6.11 years, fulfilling the updated ACR revised criteria for the classification of SLE, were recruited from the rheumatology and rehabilitation and internal medicine departments and out patient clinics of Cairo University Hospitals. Consecutive eligible patients, aged >18 years and had disease duration >1 year, were enrolled. Exclusion criteria included overlap syndrome, serum creatinine > 1.4 mg/dl, proteinuria > 0.15 g/24 hour, pregnancy, cancer, cirrhosis, history of myocardial infarction, angina, stroke or receiving insulin. Ten age and sex matched healthy volunteers served as controls with a mean age of 27.8 +/- 4.61 years. Full history taking, clinical examination and investigations were performed for all the patients. Disease activity and damage were assessed by SLEDAI and SLICC/ACR DI respectively. The Adult Treatment Panel [ATP III] criteria were used to define the presence of metabolic syndrome in SLE patients. Levels of insulin, glucose, creatinine, lipid profile as well as, ox-LDL Ab were measured in patients and control. Insulin sensitivity was estimated using the homeostatic model assessment index [HOMA-B] for beta cell function and [HOMA-IR] for peripheral tissue insulin resistance. Intima-media thickness [IMT] of the carotid artery was measured in both patients and control by ultrasonography. Patients with SLE had significantly higher mean values of HOMA-IR, HOMA-B, ox-LDL Ab and intima-media thickness [IMT]. The mean IMT in the SLE patients was 0.74 +/- 0.38 mm vs 0.25 +/- 0.09 mm in the control. Moreover, the circulating serum ox-LDL level in SLE patients was significantly higher compared to control subjects [37.18 +/- 10.85 EU/ml vs. 14.18 +/- 2.42 EU/ml, respectively]. On classifying SLE patients according to the presence or absence of metabolic syndrome, the mean ox-LDL Ab level was significantly higher in patients with metabolic syndrome [n = 11] compared to those without metabolic syndrome [n = 19]. While, no statistically, significant difference was observed between both groups either in SLE disease activity index [SLEDAI], damage index [SLICC/DI], HOMA-IR, HOMA-B or IMT. Correlation of the metabolic features and IMT of the SLE patients with the studied parameters revealed a significant positive correlation between the ox-LDL and the waist-hip ratio, HOMA-IR, SLEDAI, SLICC/DI indices as well as IMT. Beta cell function significantly negatively correlated with the dose of administered steroids. Furthermore,' IMT significantly positively correlated with the SLEDAI and SLICC/DI respectively. It could be concluded that serum ox-LDL is altered in SLE patients especially with metabolic syndrome and is correlated with insulin resistance and atherosclerosis as well as SLE activity and damage indices. Additionally, IMT is increased in SLE patients. Both serum ox-LDL level and IMT measurement are recommended in SLE patients and could be used as useful markers for predicting future cardiovascular events especially in the absence of symptoms of CVD