140 - PROMOTING ENDOTHELIAL CELL HEALTH AFTER KAWASAKI DISEASE: PEACH STUDY

Background:  Coronary artery aneurysm (CAA) due to KD vasculitis may lead to devastating cardiovascular complications. The long-term effects of inflammation caused by KD have yet to be fully characterized. Statins are known to have anti-inflammatory, anti-oxidant, and endothelial-repairing properties. Studies in adult cardiovascular disease suggest that statins significantly reduce mortality and major coronary events. There are few studies evaluating statin use in KD patients with CAA. We investigated the effect of atorvastatin treatment for improving endothelial cell function in pediatric patients with persistent CAA.


Methods:  KD patients aged at least 8 years old with persistent CAA were enrolled in this study at Rady Children's Hospital San Diego. We obtained blood samples and evaluated endothelial cell function non-invasively by flow-mediated vasodilation in the brachial artery using EndoPAT system before and 3-6 months after initiating atorvastatin therapy. We assessed vascular inflammation and myocardial fibrosis biomarkers using ELISA. We analyzed plasma proteins on the SOMAscan platform that utilizes the SOMAmer (Slow Off-rate Modified Aptamer) reagents consisting of short single-stranded DNA and can accurately resolve over 6,000 proteins. We will analyze plasma cell-free RNA (cfRNA) that is released from cells and reflects tissue damage and immune dynamics. Plasma samples will also be collected following one and two years of atorvastatin therapy. Paired data was analyzed by the paired t-Test or Wilcoxon signed rank test.


Results:  We evaluated endothelial cell function pre and post atorvastatin by EndoPAT in 6 patients (5 male and 1 female, median age 14.5 years, range: 10-20). Natural log Reactive Hyperemia Index (LnRHI) was not significantly different between pre and post atorvastatin (median [IQR]: Pre 0.72[0.47-1.09], Post 0.52[0.38-0.78], p=0.2). Pre and post atorvastatin plasma from 7 patients showed no significant difference in a paired analysis for calprotectin (S100A8/S100A9 heterodimer), galectin-3, GDF-15, ST2, TIMP-1 and pentraxin 3. In the preliminary analysis of SOMAscan data, post-atorvastatin samples had decreased matrix metalloproteinase 3 (MMP3) (unadjusted P=0.001) and apolipoprotein E3 and E4 (unadjusted P=0.006, 0.04, respectively) and increased vascular endothelial growth factor (VEGF) (unadjusted P=0.06) Analysis of cfRNA is in progress.


Conclusion:  This is the first study examining the potential benefit of statin therapy for KD patients with persistent CAA. The short time interval in this study may have precluded finding robust changes. A longer-term study of these same individuals is in progress. This study could change how we care for children with arterial damage after KD to improve their cardiovascular health.