Pitavastatin Reduces Elevated IL-18 levels in Japanese Subjects with Hypercholesterolemia: Sub-analysis of Kansai Investigation of Statin for Hyperlipidemic Intervention in Metabolism and Endocrinology (KISHIMEN)

Aim: Pitavastatin significantly improved lipid profiles and reduced serum high-sensitivity C-reactive protein (hs-CRP) levels in a multi-center and prospective study. The aim of this study was to explore the effect of pitavastatin on serum levels of another inflammatory biomarker, interleukin-18 (IL-18), in a sub-analysis of the previous multi-center prospective study. Methods: The subjects were 83 patients derived from the KISHIMEN study. Pitavastatin (1-2 mg/day) was administered for 12 months. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), remnant-like particle cholesterol (RLP-C), triglycerides (TG), IL-18, and high sensitivity C-reactive protein (hs-CRP) levels were measured. Results: TC, LDL-C, and RLP-C levels were significantly reduced by 18.3%, 30.1%, and 21.0% (mean values) at 12 months after pitavastatin administration. TG levels were decreased by 9.8% in subjects whose basal TG levels were above 150 mg/dL. HDL-C levels were significantly increased at 6 months (11.9%). Pitavastatin did not significantly alter IL-18 levels in overall subjects, but reduced IL-18 levels in the highest quartile by 24.5% (median value) at 12 months. Pitavastatin significantly reduced hs-CRP levels by 28.6% in overall subjects and by 62.4% in the highest quartile at 12 months. There was a significant correlation between IL-18 and hs-CRP at baseline after both values were transformed into logarithms (Pearson's correlation coefficient, r = 0.259, p = 0.0181); however, percent changes in these levels were not significantly correlated. Conclusion: Pitavastatin significantly improves lipid profiles, and reduces enhanced inflammation monitored by IL-18, as well as by hs-CRP, in hypercholesterolemic subjects.