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Platelet-activating factor-acetylhydrolase and other novel risk and protective factors for cardiovascular disease in systemic lupus erythematosus.

OBJECTIVE
There is an important inflammatory component to atherosclerosis and cardiovascular disease (CVD). It is therefore interesting that the risk of CVD is high in inflammatory diseases such as systemic lupus erythematosus (SLE). In this study, we investigated nontraditional risk factors for the development of CVD in patients with SLE.


METHODS
Twenty-six women (mean age 52 years) with SLE and a history of CVD 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). Serum levels of several novel nontraditional risk and protective factors were determined: heat-shock protein (HSP)-related factors (Hsp60, Hsp70, anti-human Hsp60, anti-human Hsp70, and anti-mycobacterial Hsp65), platelet-activating factor-acetylhydrolase (PAF-AH) activity, secretory phospholipase A(2) GIIA (sPLA(2)), and anti-endothelial cell antibody (AECA). The intima-media thickness and the presence of plaques in the common carotid arteries were determined by B-mode ultrasound as a surrogate measure of atherosclerosis.


RESULTS
Levels of PAF-AH, but not HSP-related factors, AECA, or sPLA(2), were significantly increased in SLE cases. Only PAF-AH discriminated between SLE cases and SLE controls (P = 0.005). PAF-AH was significantly associated with low-density lipoprotein (LDL) cholesterol and total cholesterol in the SLE cases (r = 0.50, P = 0.0093 and r = 0.54, P = 0.0045), but not in either control group.


CONCLUSION
The increased levels of PAF-AH in SLE cases and the association between PAF-AH and LDL cholesterol adds support to the notion that PAF-AH may promote atherothrombosis in SLE. The role of HSPs in CVD is complex, since anti-Hsp65 appears to be associated with the presence of CVD, whereas Hsp70 might protect against it. In this cross-sectional study, levels of HSP-related factors, AECA, and sPLA(2) were not associated with CVD in SLE.