Peripheral Endothelial (Dys)Function, Arterial Stiffness and Carotid Intima-Media Thickness in Patients after Kawasaki Disease: A Systematic Review and Meta-Analyses

Kawasaki disease (KD) is a systemic pediatric vasculitis. Its main complication is the development of coronary arterial aneurysms (CAA), causing an increased risk for ischemia and myocardial infarction. It is unclear whether KD patients, apart from the presence of CAA, have an increased cardiovascular disease (CVD) risk due to the previous systemic vasculitis. The aim of this study was to systematically review and meta-analyse the literature regarding surrogate markers for CVD risk in KD patients. Medline and Embase were searched for articles comparing endothelial dysfunction (flow-mediated dilation, nitroglycerin-mediated dilation and peripheral arterial tonometry), vascular stiffness (stiffness index, pulse wave velocity) and carotid intima-media thickness (cIMT) between patients and controls. Two investigators assessed the articles for eligibility and evaluated quality. Thirty studies were included. For all outcomes, moderate to high heterogeneity between studies was found. Most studies reported a decreased flow-mediated dilation in the whole KD- and CAA-positive group compared to controls, while data on CAA-negative patients were conflicting. The stiffness index was increased in the majority of studies evaluating the whole KD- and CAA-positive group, but not in most studies on CAA-negative patients. Mean cIMT was neither significantly increased in the whole KD-group nor in the CAA-positive group nor in most studies studying CAA-negative patients. Studies measuring maximum cIMT were conflicting. Literature suggests that surrogate markers for CVD risk in KD patients are increased in CAA-positive but not in CAA-negative patients. This may indicate that CAA-positive patients should be monitored for CVD in later life. The results of this review have to be interpreted with care due to substantial heterogeneity between studies and methodological limitations, as well as the lack of long-term follow-up studies