Aim: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. . Recent studies have elucidated the molecular mechanisms underlying intestinal cholesterol absorption, another potential therapeutic target for hypercholesterolemia. In 2000, Niemann-Pick C1 like 1 (NPC1L1), a transporter protein important for intestinal cholesterol absorption, was cloned. NPC1L1 is composed of 1,359 amino acids, possesses 13 transmembrane spanning
IntroductionElevated low density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular diseases and its two sources, i.e., de novo synthesis in the liver and the absorption of dietary and bilialy cholesterol in the intestine, have offered important targets for the treatment of hypercholesterolemia. HMGCoA reductase inhibitors (statins), which target choAddress for correspondence: Shinya Hiramitsu, Fujita Ezetimibe STudy Assembly (FESTA) investigators group, Shiroshita-cho 2-35, Minami-ku, Nagoya 457-0047, Japan E-mail: hirazy@fujita-hu.ac. , together with a growing body of evidence that relates cholesterol absorption to the risk of cardiovascular events 4,5) , has made investigators more aware of the importance of controlling cholesterol absorption for the prevention of these cardiovascular events. Some investigators have reported increased intestinal cholesterol absorption in US and/or European individuals with a history of coronary artery disease 6) , obesity 7) , or type 2 diabetes mellitus 8) , although the relevance of this alteration to these and other pathologies remains to be determined.Based on these considerations, we evaluated the clinical benefit of ezetimibe and its effect on surrogate markers of cholesterol absorption and synthesis in Japanese patients with hypercholesterolemia in order to establish more efficient lipid-lowering therapy.
MaterialsBetween June and December 2007, patients who presented to the outpatient clinic of Fujita Ezetimibe Study Assembly were enrolled if they had not achieved the LDL-C goal levels recommended in the 2007 Guideline of the Japan Atherosclerosis Society (JAS) 9) despite diet and exercise without anti-dyslipidemic agents for at least 4 weeks (ezetimibe monotherapy group) or had not achieved the LDL-C management goal levels despite at least 4 weeks of statin therapy (co-administration with ezetimibe and any statin). The study protocol was approved by the Fujita Health University Ethics Committee and all patients gave written informed consent.
MethodsAt enrollment, all patients were examined ...