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Review SLE, atherosclerosis and cardiovascular disease. 2005
Frostegård J. · Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden. · J Intern Med. · Pubmed #15910552 No free full text.
Abstract: Atherosclerosis is an inflammatory disease and the major cause of cardiovascular disease (CVD) in general. Atherosclerotic plaques are characterized by the presence of activated immune competent cells, but antigens and underlying mechanisms causing this immune activation are not well defined. During recent years and with improved treatment of acute disease manifestations, it has become clear that the risk of CVD is very high in a prototypic autoimmune disease, systemic lupus erythematosus (SLE). SLE-related CVD and atherosclerosis are important clinical problems but may in addition also shed light on how immune reactions are related to premature atherosclerosis and atherothrombosis. A combination of traditional and nontraditional risk factors, including dyslipidaemia (and to a varying degree hypertension, diabetes and smoking), inflammation, antiphospholipid antibodies (aPL) and lipid oxidation are related to CVD in SLE. Premature atherosclerosis in some form leading to atherothrombosis is likely to be a major underlying mechanism, though distinctive features if any, of SLE-related atherosclerosis when compared with 'normal' atherosclerosis are not clear. One interesting possibility is that factors such as inflammation or aPL make atherosclerotic lesions in autoimmune disease more prone to rupture than in 'normal' atherosclerosis. Whether premature atherosclerosis is a general feature of SLE or only affects a subgroup of patients remains to be demonstrated. Treatment of SLE patients should also include a close monitoring of traditional risk factors for CVD. In addition, attention should also be paid to nontraditional risk factors such as inflammation and SLE-related factors such as aPL. Hopefully novel therapeutic principles will be developed that target the causes of the inflammation and immune reactions present in atherosclerotic lesions.
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Article Elevated triglycerides and low levels of high-density lipoprotein as markers of disease activity in association with up-regulation of the tumor necrosis factor alpha/tumor necrosis factor receptor system in systemic lupus erythematosus. free! 2003
Svenungsson E, Gunnarsson I, Fei GZ, Lundberg IE, Klareskog L, Frostegård J. · Department of Medicine, Karolinska Institute, Stockholm, Sweden. · Arthritis Rheum. · Pubmed #13130473 links to free full text
Abstract: OBJECTIVE: To investigate how blood lipid levels are related to disease activity, clinical characteristics, and serum levels of tumor necrosis factor alpha (TNF alpha) and its soluble type 1 and 2 receptors, sTNFR1 and sTNFR2, in systemic lupus erythematosus (SLE). METHODS: Fasting blood samples were obtained from an unselected cohort of SLE patients at Karolinska Hospital (n = 208, mean +/- SD age 45.7 +/- 14.2 years). Disease activity was estimated using the SLE Disease Activity Measure (SLAM). Levels of circulating TNF alpha, sTNFR1, and sTNFR2 were determined by enzyme-linked immunosorbent assay. Blood lipid levels obtained after overnight fasting were analyzed by routine chemistry. RESULTS: Triglyceride (TG) levels were associated with the SLAM score (r = 0.48, P < 0.0001) and with the activities of TNF alpha (r = 0.29, P = 0.0001), sTNFR1 (r = 0.38, P < 0.0001), and sTNFR2 (r = 0.40, P < 0.0001). High-density lipoprotein (HDL) levels were negatively associated with the SLAM score (r = -0.27, P = 0.0003) and with the activities of TNF alpha (r = -0.15, P = 0.04) and sTNFR2 (r = -0.19, P = 0.01). High levels of TGs, total cholesterol, TNF alpha, sTNFR1, and sTNFR2 all showed close correlations with the presence of nephritis and arterial disease (P < 0.05). In multiple logistic regression models, the TNF alpha activity and TG levels were independent determinants (P = 0.003 for both) of active disease (SLAM score > or =7). CONCLUSION: Dyslipoproteinemia with high TG/low HDL levels correlates with disease activity in SLE, and enhanced activity in the TNFalpha/sTNFR system seems to be an important underlying factor. Both dyslipoproteinemia and enhanced activity of the TNF alpha system are closely related to cardiovascular and renal manifestations in SLE, and thus both may serve as markers of more severe disease.
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