The effects of ezetimibe on surrogate markers of cholesterol absorption and synthesis in Japanese patients with dyslipidemia.
OBJECTIVE
To demonstrate the clinical benefit of inhibiting intestinal cholesterol absorption, we evaluated the effects of ezetimibe on surrogate markers of cholesterol absorption and synthesis, lipid and glucose metabolism, and markers of obesity and inflammation.


METHODS
A total of 120 patients with dyslipidemia (46 men; mean age 66.5 years), who had not achieved the low density lipoprotein cholesterol (LDL-C) goal recommended by the Japan Atherosclerosis Society Guideline despite diet and exercise or any statin therapy, were enrolled and additionally treated with ezetimibe (10 mg/day) for 12 weeks.


RESULTS
Compared to the baseline, LDL-C was reduced by 19.2% (p<0.001) after ezetimibe monotherapy and by 24.7% (p<0.001) after co-administration with ezetimibe and any statin. Ezetimibe therapy decreased cholesterol absorption markers and increased a cholesterol synthesis marker. Treatment with ezetimibe reduced the fasting serum insulin level (p<0.05) and HbA1c (p<0.05), increased serum adiponectin (p<0.01), and showed a significant decrease of high-sensitive C-reactive protein (hsCRP, p<0.01). No adverse events occurred during the study.


CONCLUSIONS
Thus, cholesterol absorption inhibition by ezetimibe is an important therapeutic strategy since LDL-C and cholesterol absorption markers had a positive correlation. Ezetimibe not only reduced the serum LDL-C level but also improved glucose metabolism as well as obesity and inflammation markers. These findings support the benefit of ezetimibe as a new option for the treatment of dyslipidemia.
Hiramitsu
Shinya
S
Fujita Ezetimibe STudy Assembly (FESTA) investigators group, Nagoya 457-0047, Japan.
Ishiguro
Yoshiaki
Y
Matsuyama
Hiroyuki
H
Yamada
Kenji
K
Kato
Kazuo
K
Noba
Manji
M
Uemura
Akihisa
A
Yoshida
Satoshi
S
Matsubara
Yoshiro
Y
Kani
Atsushi
A
Hasegawa
Kazuo
K
Hishida
Hitoshi
H
Ozaki
Yukio
Y
D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D044466:Asian People; D001384:Azetidines / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000096:biosynthesis / Q000097:blood*; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D000069438:Ezetimibe; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000453:epidemiology; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001384:Azetidines; D015415:Biomarkers; D001786:Blood Glucose; D002097:C-Reactive Protein; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000069438:Ezetimibe; D006442:Glycated Hemoglobin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D014280:Triglycerides