Ezetimibe monotherapy ameliorates vascular function in patients with hypercholesterolemia through decreasing oxidative stress.
OBJECTIVE
Ezetimibe, an inhibitor of cholesterol intestinal absorption, is a lipid lowering agent. However, anti-atherogenic effects of ezetimibe have not been fully elucidated. Therefore, the objective in this study was to clarify the vascular protective effects of ezetimibe in patients with hypercholesterolemia.


METHODS
Ezetimibe was administered to 20 patients with hypercholesterolemia (group E), and 20 age- and sex-matched patients with hypercholesterolemia were followed as controls (group C). Difference in metabolic profiles and cardiovascular surrogate markers before ezetimibe treatment and after 12 weeks of ezetimibe treatment were statistically evaluated.


RESULTS
Ezetimibe treatment significantly reduced serum levels of low-density lipoprotein cholesterol (LDL-C) and malondialdehyde-modified low-density lipoprotein (MDA-LDL). In addition, the values of body mass index, body weight, waist circumference, plasma HbA1c and urinary albumin were significantly decreased in group E compared to those in group C. On the other hand, high-density lipoprotein cholesterol (HDL-C) and adiponectin levels were significantly increased in group E compared to those in group C. The values of brachial-ankle pulse wave velocity (ba-PWV), mean arterial blood pressure (m-ABP), and % of flow-mediated dilation (FMD) were significantly improved in group E. Furthermore, ultrasonic studies demonstrated amelioration of the vascular stiffness of common carotid arteries in group E but not in group C. These vascular protective effects of ezetimibe were statistically correlated with the decreased values of MDA-LDL and MDA-LDL-to-LDL-C ratio but not with those of LDL-C.


CONCLUSIONS
Ezetimibe has a lipid lowering-independent vascular protective effect in patients with hypercholesterolemia through decreasing oxidative stress.
Department of Cardiovascular Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. hirotsugu.kurobe@clin.med.tokushima-u.ac.jp
Hirotsugu
H
Kurobe
Ken-ichi
K
Aihara
Mayuko
M
Higashida
Yoichiro
Y
Hirata
Masako
M
Nishiya
Yuki
Y
Matsuoka
Tamotsu
T
Kanbara
Taisuke
T
Nakayama
Hajime
H
Kinoshita
Mikio
M
Sugano
Eiki
E
Fujimoto
Ayako
A
Kurobe
Noriko
N
Sugasawa
Takashi
T
Kitaichi
Masashi
M
Akaike
Masataka
M
Sata
Toshio
T
Matsumoto
Tetsuya
T
Kitagawa
D000368:Aged; D001384:Azetidines / Q000494:pharmacology / Q000627:therapeutic use*; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D000069438:Ezetimibe; D006801:Humans; D006937:Hypercholesterolemia / Q000503:physiopathology*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*
D001384:Azetidines; D008055:Lipids; D000069438:Ezetimibe