SAT0311 Prolonged exposure to antiphospholipid antibodies is associated with endothelial dysfunction in patients with systemic lupus erythematosus

Abstract

Background: Antiphospholipid syndrome has been shown to be associated with increased cardiovascular mortality, but the role of antiphospholipid antibodies (aPL) on endothelial dysfunction remains elusive. Objectives: We investigated the association between endothelial dysfunction and aPL in systemic lupus erythematosus (SLE) patients. Methods: 188 SLE patients and 62 controls were enrolled. Endothelial function was measured by flow-mediated dilatation (FMD). Cardiovascular risk factors were assessed and quarterly measurement of anti-cardiolipin (aCL) and anti-β2 glycoprotein I Ab were used to calculate time-integrated values throughout disease duration. Circulating endothelial progenitor cell (EPC), defined by CD34+/KDR+ mononuclear cells, was quantified by flow cytometry. Results: Median FMD was significantly lower in SLE patient than in controls (6.9 versus 9.3%, P<0.001). In univariate analysis, older age, hypertension, thrombocytopenia, and persistent positive lupus anticoagulant (LAC) were associated with decreased FMD in SLE patients (P=0.021, P=0.011, P=0.004, and P=0.028). Time-integrated aCL value (TI-aCL), but not a single value, was correlated with decreased FMD (P=0.001). Multivariate analysis showed that hypertension and TI-aCL were independent factors for decreased FMD (P=0.027, P=0.008); addition of positive LAC increased the adjusted probability of decreased FMD (P=0.023). FMD was correlated with EPC number (γ=0.342, P=0.005) and TI-aCL was also an independent factor of reduced EPC after multiple adjustment (P=0.019). The predicted probability of endothelial dysfunction at median EPC level was higher in group with high TI-aCL than in group with low TI-aCL (P=0.004). Conclusions: Cumulative burden of aPL was closely associated with endothelial dysfunction in SLE patients, which was mediated in part by reduction of EPC.