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


METHODS
We 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).


RESULTS
A 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.


CONCLUSIONS
The 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.
Hamaoka
Akiko
A
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan. ahamaoka@koto.kpu-m.ac.jp
Hamaoka
Kenji
K
Yahata
Tomoyo
T
Fujii
Maiko
M
Ozawa
Seiichiro
S
Toiyama
Kentaro
K
Nishida
Masashi
M
Itoi
Toshiyuki
T
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D002648:Child; D004730:Endothelium, Vascular; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000652:urine; D018384:Oxidative Stress; D011674:Pulse; D013997:Time Factors
D015415:Biomarkers; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D009569:Nitric Oxide; D000077340:Fluvastatin; D002097:C-Reactive Protein