Ezetimibe ameliorates metabolic disorders and microalbuminuria in patients with hypercholesterolemia.
OBJECTIVE
Ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, has been shown to reduce the intestinal absorption of cholesterol. We investigated whether it also has beneficial effects on metabolic disorder and/or renal insufficiency in patients with hypercholesterolemia.


METHODS
Ezetimibe was administered to 38 Japanese patients with hypercholesterolemia to obtain appropriate low-density lipoprotein cholesterol (LDL-chol) levels. Age- and sex-matched patients with hypercholesterolemia (n=38) were the controls. We evaluated the effects of ezetimibe before and 4 to 8 weeks after ezetimibe treatment.


RESULTS
Ezetimibe significantly decreased LDL-chol levels and metabolic syndrome-related factors, including body weight, waist circumference, blood pressure; homeostasis model assessment insulin resistance (HOMA-IR), and urinary albumin excretion, were significantly reduced. In addition, it decreased the level of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha, the urinary excretion of 8-hydroxy-2'-deoxyguanosine, a parameter of oxidative stress, and increased the urinary excretion of nitrate and nitrite (NOx). In the controls we observed no such changes. Excepting the decrease in the serum TNF-alpha level, the effects of ezetimibe were not correlated with decreased LDL-chol levels.


CONCLUSIONS
Ezetimibe ameliorated the status of metabolic syndrome and microalbuminuria, reduced inflammation and oxidative stress, and increased nitric oxide bioavailability in a LDL-chol reduction-dependent and -independent manner.
Department of Cardiovascular Medicine, The University of Tokushima Graduate School of Health Biosciences, Tokushima, Japan. syagi@clin.med.tokushima-u.ac.jp
Shusuke
S
Yagi
Masashi
M
Akaike
Ken-ichi
K
Aihara
Takashi
T
Iwase
Kazue
K
Ishikawa
Sumiko
S
Yoshida
Yuka
Y
Sumitomo-Ueda
Kenya
K
Kusunose
Toshiyuki
T
Niki
Koji
K
Yamaguchi
Kunihiko
K
Koshiba
Yoichiro
Y
Hirata
Munkhbaatar
M
Dagvasumberel
Yoshio
Y
Taketani
Noriko
N
Tomita
Hirotsugu
H
Yamada
Takeshi
T
Soeki
Tetsuzo
T
Wakatsuki
Toshio
T
Matsumoto
Masataka
M
Sata
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000419:Albuminuria / Q000175:diagnosis / Q000188:drug therapy*; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001384:Azetidines / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D008078:Cholesterol, LDL / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications* / Q000188:drug therapy* / Q000652:urine; D008297:Male; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000652:urine; D024821:Metabolic Syndrome / Q000378:metabolism; D008875:Middle Aged; D009566:Nitrates / Q000737:chemistry; D009573:Nitrites / Q000737:chemistry; D018384:Oxidative Stress; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002097:C-Reactive Protein; D000069438:Ezetimibe; D003849:Deoxyguanosine