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

Abstract

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; 52±8.2 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 (TNFα) activity, were identified as a novel discriminator for SLE‐related CVD. This supports our hypothesis that SLE patients with enhanced systemic TNFα activity are at high risk of developing CVD.