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)

Yoshio Fujioka; Akira Fukuda; Tatsuro Ishida; Shinji Kagimoto; Yoshio Nakamura; Akane Iwakura; Kyoko Hara; Taizo Yamamoto; Akira Kuroe; Michihiro Ohya; Shinpei Fujimoto; Yoshiyuki Hamamoto; Sachiko Honjo; Hiroki Ikeda; Koichiro Nabe; Kinsuke Tsuda; Ataru Taniguchi; Kiyoshi Tanaka; Hiroyuki Koshiyama; Noriaki Kume; Ken-ichi Hirata

doi:10.5551/jat.5942

Original Article

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)

Yoshio Fujioka, Akira Fukuda, Tatsuro Ishida, Shinji Kagimoto, Yoshio Nakamura, Akane Iwakura, Kyoko Hara, Taizo Yamamoto, Akira Kuroe, Michihiro Ohya, Shinpei Fujimoto, Yoshiyuki Hamamoto, Sachiko Honjo, Hiroki Ikeda, Koichiro Nabe, Kinsuke Tsuda, Ataru Taniguchi, Kiyoshi Tanaka, Hiroyuki Koshiyama, Noriaki Kume, Ken-ichi Hirata

Author information

Yoshio Fujioka
Division of Clinical Nutrition, Faculty of Nutrition, Kobe Gakuin University.
Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine.
Akira Fukuda
Department of Cardiology, Osaka Saiseikai Nakatsu Hospital.
Tatsuro Ishida
Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine.
Shinji Kagimoto
Kagimoto Diabetes Clinic.
Yoshio Nakamura
Division of Diabetes & Endocrinology, Department of Internal Medicine, Hyogo Prefectual Amagasaki Hospital.
Akane Iwakura
Division of Diabetes & Endocrinology, Department of Internal Medicine, Hyogo Prefectual Amagasaki Hospital.
Kyoko Hara
Division of Diabetes & Endocrinology, Department of Internal Medicine, Hyogo Prefectual Amagasaki Hospital.
Taizo Yamamoto
Department of Endocrinology and Diabetes, Kyoto-Katsura Hospital.
Akira Kuroe
Department of Internal Medicine, Hikone Municipal Hospital.
Michihiro Ohya
Division of Diabetes and Clinical Nutrition, Kansai Electric Power Hospital.
Shinpei Fujimoto
Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University.
Yoshiyuki Hamamoto
Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University.
Center for Diabetes and Endocrinology, The Tazuke Kofukai Foundation Medical Research Institute Kitano Hospital.
Sachiko Honjo
Center for Diabetes and Endocrinology, The Tazuke Kofukai Foundation Medical Research Institute Kitano Hospital.
Hiroki Ikeda
Center for Diabetes and Endocrinology, The Tazuke Kofukai Foundation Medical Research Institute Kitano Hospital.
Koichiro Nabe
Center for Diabetes and Endocrinology, The Tazuke Kofukai Foundation Medical Research Institute Kitano Hospital.
Kinsuke Tsuda
Graduate School of Human and Enviromental Studies, Kyoto University.
Ataru Taniguchi
Division of Diabetes and Endocrinology, Kyoto Preventive Medical Center.
Kiyoshi Tanaka
Department of Nutrition, Kyoto Women's University.
Hiroyuki Koshiyama
Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University.
Center for Diabetes and Endocrinology, The Tazuke Kofukai Foundation Medical Research Institute Kitano Hospital.
Noriaki Kume
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University.
Ken-ichi Hirata
Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine.

Keywords: statin, cholesterol, inflammation, interleukin-18 (IL-18), high sensitivity C-reactive protein(hs-CRP)

JOURNAL OPEN ACCESS

2011 Volume 18 Issue 1 Pages 8-15

DOI https://doi.org/10.5551/jat.5942

View "Advance Publication" version (October 6, 2010).

Details

Abstract

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.

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