| Systemic Lupus Erythematosus (SLE) is a chronic inflammatory disease of unknown cause which can affect any organs. Studies have reported an increased prevalence of cardiovascular disease (CVD) in these patients. We performed a series of studies to elucidate the interaction between microalbuminuria, dyslipidaemia, hyperhomocysteinemia, oxidative stress and immune dysregulation from the underlying disease in order to understand the accelerated atherosclerotic process in SLE.;My first step was to elucidate the prevalence and metabolic abnormalities in SLE patients with microalbuminuria. Twenty percent of patients were found to have microalbuminuria, which was associated with higher mean arterial pressure, total plasma antioxidant and homocysteine levels.;Next, we recruited 12 SLE patients and 15 controls and gave them oral methionine loading to achieve acute hyperhomocysteinemia. After oral methionine loading, von Willebrand factor (vWF) levels increased significantly in both groups. The increase in vWF was apparently more pronounced in SLE (20%) compared to controls (8%). Fibrinogen binding to platelets increased significantly only in SLE patients.;We then evaluated the effects of long-term antioxidant vitamins. The plasma malondialdehyde level was significantly decreased after treatment in the vitamin group. Other oxidative stress markers and antioxidant levels and endothelial function remained unchanged in both groups.;We then proceeded to study the relative effect of antimalarial agents on fasting lipid fractions in patients with active SLE. Total cholesterol, very low-density lipoprotein cholesterol, and low density lipoprotein cholesterol levels were significantly lower in patients taking antimalarial agents, particularly for those patients taking concomitant prednisone. In the last study, we demonstrated that hydroxychloroquine had no significant effect on the serum lipid profile in these lupus patients with mild or inactive disease.;From this series of studies, we conclude that microalbuminuria may represent a novel risk factor in SLE, and lupus patients are more susceptible to endothelial dysfunction caused by hyperhomocysteinemia. The use of antimalarial agents is beneficial for lupus patients with active disease on corticosteroid, and antioxidant vitamins are useful in lowering the oxidative stress markers but do not affect the endothelial function. The results highlight the importance of targeting the known modifiable risk factors in order to prevent premature atherosclerosis in SLE patients. |
