Endothelial function and markers of endothelial activation in relation to cardiovascular disease in systemic lupus erythematosus

Objective: Cardiovascular disease (CVD) is common in patients with systemic lupus erythematosus (SLE) although it is not clear whether an increased risk of CVD is a general feature of SLE or whether it applies only to a subgroup of patients. Our objective was to evaluate endothelial function and markers of endothelial activation in relation to CVD in SLE. Methods: Twenty-six women with SLE and previous CVD (SLE/CVD cases, defined as objectively verified angina pectoris, myocardial infarction, cerebral infarction, or intermittent claudication; 528.2 years) were compared with age-matched SLE women without CVD (SLE controls) and population control women. Flow-mediated dilatation (FMD) of the brachial artery after reactive hyperaemia and nitroglycerin-mediated dilatation (NMD) after sublingual nitroglycerin administration were determined by ultrasound. Soluble thrombomodulin (sTM) and soluble vascular cellular adhesion molecule-1 (sVCAM-1) were measured by enzyme-linked immunosorbent assay (ELISA). Results: FMD and NMD levels did not differ between SLE controls and population controls. In SLE cases FMD and NMD were not assessed because of interference with nitro-related medication. sVCAM-1 discriminated between SLE cases, SLE controls, and population controls (ng/mL; 814 +/- 221 vs. 545 +/- 214 vs. 401 +/- 189, p < 0.01), whereas sTM (ng/mL; 5.2 +/- 2.8 vs. 4.2 +/- 1.9 vs. 3.0 +/- 0.5) differed between both SLE groups and controls (p < 0.05). Conclusion: In this study SLE women free of CVD had good endothelial function (FMD), a possible marker of protection from lupus-related CVD. In addition, high levels of sVCAM-1, associated with systemic tumour necrosis factor-alpha (TNF alpha) activity, were identified as a novel discriminator for SLE-related CVD. This supports our hypothesis that SLE patients with enhanced systemic TNF alpha activity are at high risk of developing CVD.