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Non-traditional risk and protective factors for cardiovascular disease in systemic lupus erythematosus
Arthritis Research & Therapy volume 7, Article number: P122 (2005)
There is an important inflammatory and autoimmune component to atherosclerosis and cardiovascular disease (CVD). It is therefore interesting that the risk of CVD is so exceedingly high in patients with systemic lupus erythematosus (SLE).
To investigate the role of non-traditional risk and protective factors for CVD related to inflammation and immune activation in SLE-associated CVD.
Twenty-six women (52 ± 8.2 years) with SLE and a history of CVD (SLE cases) were compared with 26 age-matched women with SLE and no clinical manifestations of CVD (SLE controls) and 26 age-matched healthy women (population controls). As a surrogate measure of atherosclerosis, common carotid intima-media thickness and plaque occurrence were detected by B-mode ultrasound. Circulating levels of oxidized low-density lipoprotein (LDL) were measured by a mAb-4E6-based competition ELISA. Several novel non-traditional risk factors identified by us and others were determined in serum: heat shock protein (HSP)-related factors (Hsp60, Hsp70 and anti-human Hsp60, anti-human Hsp70 and anti-mycobacterial Hsp65 antibody levels), platelet activating factor-acetylhydrolase activity (PAF-AH) and secretory phospholipase A2 GIIA (sPLA2). Antibodies against endothelial cells (aEC) were measured by in-house ELISA.
The circulating levels of oxidized LDL and activity levels of PAF-AH, but not HSP-related measurements, aEC antibodies or sPLA2, were significantly raised in SLE cases. Oxidized LDL levels and PAF-AH discriminated between SLE controls and SLE cases (P = 0.0282 or P = 0.008, respectively). PAF-AH was significantly associated with LDL and cholesterol among SLE/CVD (r = 0.50, P = 0.009 and r = 0.54, P = 0.004), but not in the other groups tested.
The difference in oxidized LDL levels between SLE cases and SLE controls may indicate that increased LDL modification by oxidation is one the underlying factors implicated in SLE-related CVD. The association between PAF-AH and LDL adds support to the notion that PAF-AH, which binds to LDL, might contribute to atherogenesis in SLE patients. We cannot exclude that PAF-AH is simply a secondary marker of other as yet unknown processes. The role of HSP-related measurements in CVD in general is complex, since aHSP65 appears to be atherogenic while HSP70 may be protective. In the present cross-sectional study, the HSP-related measurements and those of aEC and sPLA2 were not associated with SLE.
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Cederholm, A., Svenungsson, E., Stengel, D. et al. Non-traditional risk and protective factors for cardiovascular disease in systemic lupus erythematosus. Arthritis Res Ther 7, P122 (2005). https://doi.org/10.1186/ar1643
- Systemic Lupus Erythematosus
- Systemic Lupus Erythematosus Patient
- Secretory Phospholipase
- Hsp65 Antibody
- Systemic Lupus Erythematosus Case