Effects of HMG-CoA reductase inhibitors on continuous post-inflammatory vascular remodeling late after Kawasaki disease

SummaryBackgroundIn Kawasaki disease (KD), it has been clinically and experimentally reported that post-inflammatory vascular remodeling would induce the development of arteriosclerosis or early onset of atherosclerosis in the future. The effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on continuous vascular remodeling late after Kawasaki disease were clinically evaluated.Patients and methodsWe enrolled and treated a total of 11 KD patients (age range, 7–25 years) with fluvastatin (0.5–0.7 mg/kg/day) for 12 months. All of them had significant coronary aneurysmal or stenotic lesions and more than 3 of the following 5 abnormal findings: reduced %flow-mediated dilatation (%FMD), reduced urinary NOx, elevated high-sensitivity C-reactive protein (hs-CRP), reduced urinary 8-isoprostane, and elevated brachial-ankle pulse wave velocity (baPWV; control, ≦1400 cm/s).ResultsA statistically significant improvement was observed in each biomarker after fluvastatin treatment: %FMD, from 9.29% (3.41)% to 10.55% (3.27)% (p = 0.003) after 3 months; NOx/creatinine (cre), from 1.16 (0.54) μmol/mg cre to 1.30 (0.50) μmol/mg cre (p = 0.038) after 12 months; baPWV, from 1175.4 (277.3) cm/s to 1031.8 (155.6) cm/s (p = 0.009) after 3 months; hs-CRP, from 0.073 (0.035) mg/dl to 0.028 (0.014) mg/dl (p = 0.0002) after 3 months; and 8-iso/cre, from 751.8 (241.8) pg/mg cre to 660.0 (198.5) pg/mg cre (p = 0.018) after 3 months. No adverse events were clinically observed in the patients.ConclusionsThe results of this study suggested that HMG-CoA reductase inhibitors are useful as an alternative therapeutic strategy for stabilizing continuous post-inflammatory vascular remodeling that results in the development of arteriosclerosis late after KD or early onset of atherosclerosis in the future.