Decreased Flow-mediated Dilatation in Patients with Systemic Lupus Erythematosus: a Meta-analysis

Premature atherosclerosis, the hallmark of cardiovascular diseases, has been found to be a significant cause of late deaths in systemic lupus erythematosus (SLE) patients. Therefore, early identification of atherosclerosis before the overt disease is curial for the management program of SLE. Flow-mediated dilatation (FMD%) is a reliable, noninvasive, easy to use, reproducible, and pathogenically relevant index for early atherosclerosis. In recent years, a number of studies have been performed to compare the mean FMD% difference between patients with SLE and healthy controls. However, these studies have shown inconclusive or even contradictory findings. In this study, to derive a more precise comparison of FMD% difference between SLE patients and healthy controls, a meta-analysis was performed. Databases were searched to identify all available studies comparing FMD% between SLE patients and healthy controls. The study eligibility criteria were cohort or case-control studies with data on both patients diagnosed with SLE and healthy controls, and use of high-resolution ultrasonography to detect FMD. Random effect meta-analysis was conducted to evaluate the overall mean FMD% difference between the two groups. Publication bias was detected by funnel plot and Egger's test. Meta-regression analysis was performed to investigate the potential influencing factors on FMD% difference. Of the 434 articles initially identified, 22 were finally included in the meta-analysis. Compared to healthy controls, SLE patients had significantly lower FMD% (standardized mean difference, -1.19; 95% CI, -1.63, -0.74; P < 0.001). There was significant heterogeneity among these studies (I (2) = 94.3%, P < 0.001), which was mainly due to variations in disease duration of SLE patients. The funnel plot showed a skewed shape, indicating a marked publication bias, which was further supported by the Egger's test (P = 0.006). However, after the correction for potential publication bias by using the trim-and-fill method, the main results for all studies combined were still significant (P < 0.001). Taken together, these findings support the current evidence on a higher cardiovascular burden in SLE and support using FMD% as a surrogate for premature atherosclerosis in SLE patients.