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Simvastatin Improves Flow-Mediated Dilation, but Reduces Adiponectin Levels and Insulin Sensitivity In Hypercholesterolemic Patients

Kwang Kon Koh, MD, Michael J. Quon, MD, PhD⁺, Seung Hwan Han, MD, Yonghee Lee, PhD^*, Jeong Yeal Ahn, MD^**, Soo Jin Kim, RN, Yesl Koh, BS and Eak Kyun Shin, MD

Cardiology, Laboratory Medicine**,
Gil Medical Center, Gachon University, Incheon, Korea; Diabetes Unit, NCCAM+,
NIH, Bethesda, Maryland, USA; Weinberg College of Arts and Sciences, Northwestern University, Evanston, Illinois, USA
Department of Statistics* Ewha Womans University, Seoul, Korea

kwangk{at}gilhospital.com

ABSTRACT

Objective: We hypothesized simvastatin may reduce adiponectin levels and insulin sensitivity in hypercholesterolemic patients.

Research Design and Methods: This was a randomized, double-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched. Thirty-two patients were given placebo and 30, 32, 31, and 31 patients were given daily simvastatin 10, 20, 40, and 80 mg, respectively during a 2 month treatment period.

Results: Simvastatin 10, 20, 40, and 80 mg significantly reduced total cholesterol (mean % changes; 27, 25, 37, and 38%), LDL cholesterol (39, 38, 52, and 54%) and apolipoprotein B levels (24, 30, 36, and 42%) and improved FMD (68, 40, 49, and 63%) after 2 months therapy when compared with baseline (P<0.001 by paired t-test) or when compared with placebo (P<0.001 by ANOVA). Simvastatin 10, 20, 40, and 80 mg significantly decreased plasma adiponectin levels (4, 12, 5, and 10%) and insulin sensitivity (determined by QUICKI) (5, 8, 6, and 6%) when compared with baseline (P<0.05 by paired t-test) or compared with placebo (P=0.011 for adiponectin and P=0.034 for QUICKI by ANOVA). However, the magnitude of these percent changes (FMD, adiponectin, and QUICKI) were not significantly different among four different doses of simvastatin therapy despite dose-dependent changes in reduction of apolipoprotein B levels.

Conclusions: Simvastatin significantly improved endothelium-dependent dilation, but reduced adiponectin levels and insulin sensitivity in hypercholesterolemic patients independent of dosage and the extent of apolipoprotein B reduction.

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