Assessment of Endothelial Dysfunction in Patients with Kawasaki Disease: A Meta-Analysis

Abstract

Background: Kawasaki disease (KD) is a well-known systemic inflammatory vasculitis. Endothelial dysfunction is one of most easily overlooked non-coronary complications of KD. Several studies have assessed endothelial dysfunction using flow-mediated dilatation (FMD), nitroglycerin-mediated dilation (NMD), and biomarkers (E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cellular adhesion molecule-1 (VCAM-1)). However, the results were inconsistent and incomplete. Methods: We searched five databases for eligible studies until March 8, 2022. The summarized weighted mean difference (WMD) with 95% confidence intervals (CIs) were estimated for FMD, NMD, and four biomarkers level between KD and healthy children. A meta-analysis with subgroup analysis was conducted. Results: 40 studies with a total of 2670 children (1665 KD patients and 1005 healthy children) were identified. During the acute phase, KD patients had lower FMD compared to the control group (WMD = –10.39, 95% CI: –13.80– –6.98). During the subacute phase, KD patients had lower FMD compared to the control group (WMD = –15.07, 95% CI: –17.61– –12.52). During the convalescence phase, KD patients had lower FMD and similar NMD compared to the control group (WMD = –4.95, 95% CI: –6.32– –3.58; WMD = –0.92, 95% CI: –2.39–0.55, respectively). During the convalescence phase, those KD patients without coronary artery lesion (CAL), with CAL, even with coronary artery aneurysm, had progressively lower FMD compared to healthy children (WMD = –3.82, 95% CI: –7.30– –0.34; WMD = –6.32, 95% CI: –7.60– –5.04; and WMD = –6.97, 95% CI: –7.99– –5.95, respectively). Compared to KD patients without CAL, those with CAL had lower FMD (WMD = –1.65, 95% CI: –2.92– –0.37). KD patients had higher levels of E-selectin, P-selectin, and ICAM-1 compared to healthy controls during different phases. KD patients had a higher level of VCAM-1 compared to healthy controls only during the acute phase (WMD = 61.62, 95% CI: 21.38–101.86). Conclusions: Endothelial dysfunction is present since the onset of KD and persists for years, confirmed by the measurement of FMD and biomarkers from different phases. An assumption is advanced that FMD impairment (the severity of endothelial dysfunction) may be positively correlated with CAL severity during the convalescence phase.