Endothelial dysfunction in systemic lupus erythematosus - a case-control study and an updated meta-analysis and meta-regression

Endothelium-dependent flow-mediated dilation (ED-FMD), a biophysical marker of endothelial dysfunction, is apparently impaired in patients with systemic lupus erythematosus (SLE) but such observation is inconsistent. Here, we assessed and compared the brachial artery ED-FMD (baED-FMD) using ultrasonography between SLE patients without cardiovascular disease and healthy controls (HC) matched for age, gender and body mass index. We then performed a comprehensive meta-analysis of case-control studies which compared baED-FMD between SLE patients and HC by determining the effect size of baED-FMD as standardized mean difference (SMD). Factors associated with the effect size were explored by mixed-model meta-regression. Seventy one SLE patients and 71 HC were studied. SLE patients had lower baED-FMD than HC (3.72 +/- 2.8% vs 4.63 +/- 3.1%, p = 0.032). Meta-analysis of 25 case-control studies involving 1,313 SLE patients and 1,012 HC with the random effects model revealed lower baED-FMD in SLE patients compared to HC (SMD -1.077, p < 0.001). The presence of diabetes mellitus (p = 0.04747), higher diastolic blood pressure (p = 0.044), renal involvement (p = 0.027) and aspirin use (p = 0.001) were associated with more discrepant baED-FMD between both groups. In conclusion, SLE patients naive of cardiovascular disease have impaired endothelial function. Diabetes mellitus, renal disease and diastolic hypertension are major contributors of endothelial dysfunction in SLE patients.