Ezetimibe ameliorates metabolic disorders and microalbuminuria in patients with hypercholesterolemia.

Abstract

AIM:

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.

CONCLUSION:

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.

• Authors: Shusuke Yagi, Masashi Akaike, Ken-ichi Aihara, Takashi Iwase, Kazue Ishikawa, Sumiko Yoshida, Yuka Sumitomo-Ueda, Kenya Kusunose, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Yoichiro Hirata, Munkhbaatar Dagvasumberel, Yoshio Taketani, Noriko Tomita, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Toshio Matsumoto, Masataka Sata
• Journal: Journal of atherosclerosis and thrombosis (J Atheroscler Thromb) Vol. 17 Issue 2 Pg. 173-80 (Feb 26 2010) ISSN: 1880-3873 [Electronic] Japan
• PMID: 20150722 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticholesteremic Agents
• Azetidines
• Cholesterol, LDL
• Nitrates
• Nitrites
• Tumor Necrosis Factor-alpha
• 8-Hydroxy-2'-Deoxyguanosine
• C-Reactive Protein
• Ezetimibe
• Deoxyguanosine

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Aged
• Albuminuria (diagnosis, drug therapy)
• Anticholesteremic Agents (pharmacology)
• Azetidines (pharmacology)
• C-Reactive Protein (metabolism)
• Case-Control Studies
• Cholesterol, LDL (metabolism)
• Deoxyguanosine (analogs & derivatives, metabolism)
• Ezetimibe
• Female
• Humans
• Hypercholesterolemia (complications, drug therapy, urine)
• Male
• Metabolic Diseases (drug therapy, urine)
• Metabolic Syndrome (metabolism)
• Middle Aged
• Nitrates (chemistry)
• Nitrites (chemistry)
• Oxidative Stress
• Tumor Necrosis Factor-alpha (metabolism)