Endothelium-dependent But Not Endothelium-independent Flow-mediated Dilation Is Significantly Reduced in Patients with Systemic Lupus Erythematosus without Vascular Events: A Metaanalysis and Metaregression

Objective. To assess whether endothelium-dependent and endothelium-independent flow-mediated dilation (FMD) are impaired in patients with systemic lupus erythematosus (SLE) with no history of vascular event; and to determine factors moderating impaired FMD in SLE. Methods. Electronic databases were searched for case-control studies that compared endothelium-dependent and/or endothelium-independent FMD at the brachial artery between SLE patients who were naive for vascular events and matched healthy controls. Effect size as standardized mean difference (SMD) and 95% confidence intervals of FMD between SLE patients and controls was pooled using the inverse variance method. Mixed-model metaregression was performed to identify potential demographic and clinical factors associated with the effect size. Results. Thirteen relevant studies involving 580 patients and 381 matched healthy controls were included. Endothelium-dependent FMD was significantly lower in SLE patients than in controls (SMD -0.832,95% CI -1.172 to -0.492, p < 0.001). Endothelium-independent FMD, however, did not differ between the 2 groups (SMD -0.179,95% CI -0.433 to 0.075, p = 0.167). Metaregression revealed that increasing age (r = 0.047, p = 0.037) and duration of SLE (r = 0.008, p = 0.024) at the time of FMD measurement significantly narrowed the difference of endothelium-dependent FMD between patients and controls; whereas sex, smoking, menopause, diabetes mellitus, body mass index, blood pressure, fasting lipid profile, C-reactive protein, and prednisolone use did not. Conclusion. Endothelium-dependent, but not endothelium-independent FMD is significantly impaired in lupus patients who are naive for vascular events. Increasing age and longer disease duration may limit the potential of endothelial reactivity as an indicator of early atherosclerosis in SLE. (First Release April 1 2011; J Rheumatol 2011;38:1296-303; doi:10.3899/jrheum.101182)