BACKGROUNDStatins and ezetimibe have been reported to change the balance of cholesterol metabolism, but few studies have been performed on Chinese patients. The aim of this study was to evaluate changes in cholesterol metabolism markers in patients with coronary heart disease.

METHODSForty-five patients with coronary heart disease were treated with 20 mg/d of simvastatin for four weeks. Subjects were then divided into two different therapy groups according to whether they reached the target values for total cholesterol and low density lipoprotein cholesterol level. Patients who reached the target values remained on simvastatin and those who did not reach the target values took a combination of simvastatin plus 10 mg/d ezetimibe until the 12th week. The concentrations of cholesterol synthesis markers (lathosterol and desmosterol) and absorption markers (campesterol and sitosterol) were measured on the 1st, 4th, and 12th week of the study by gas chromatography.

RESULTSAfter treatment with simvastatin for four weeks, the levels of total cholesterol and low density lipoprotein cholesterol decreased significantly compared to levels measured during the 1st week (P < 0.05). On the 12th week the levels of total cholesterol and low density lipoprotein cholesterol had decreased significantly (P < 0.001) compared to levels during the 4th week. By the 12th week the levels of campesterol and sitosterol in the combination group had decreased significantly (P < 0.05) compared with levels measured during the 4th week.

CONCLUSIONSCoronary heart disease patients with high cholesterol synthesis at baseline might gain a greater benefit from simvastatin treatment. Combination therapy with simvastatin plus ezetimibe in patients with low cholesterol synthesis at baseline might increase the success rate of lipid-lowering through decreasing the absorption of cholesterol.

Adult ; Aged ; Azetidines ; administration & dosage ; Cholesterol ; metabolism ; Cholesterol, LDL ; blood ; Coronary Disease ; drug therapy ; metabolism ; Drug Therapy, Combination ; Ezetimibe ; Female ; Humans ; Male ; Middle Aged ; Simvastatin ; administration & dosage

BACKGROUND AND OBJECTIVES: Ezetimibe alone does not decrease C-reactive protein (CRP) levels in hypercholesterolemic patients. However, several reports have suggested that ezetimibe might potentiate the effect of statin not only on cholesterol but also on CRP when administered together. We investigated the effect of ezetimibe on CRP levels in patients taking statins. SUBJECTS AND METHODS: Patients who had not achieved recommended low density lipoprotein-cholesterol (LDL-C) goals with statin therapy were divided into two groups, the ezetimibe group (n=60) and the control group (n=60). A third group of hypercholesterolemic patients without statin therapy was treated with statin (n=59). Patients with CRP level 10 mg/L were excluded. Lipid and CRP levels were measured before therapy commenced, and after 2 months of therapy. RESULTS: Ezetimibe decreased cholesterol and LDL-C levels by 20.2% (p=0.000) and 28.1% (p=0.000) respectively. However, ezetimibe did not reduce CRP levels (from 0.83+/-0.68 to 1.14+/-1.21 mg/dL, p=0.11). CRP levels remained unchanged in the control group (p=0.42). In contrast, statin lowered CRP levels (from 0.82+/-0.73 to 0.65+/-0.57 mg/dL, p=0.008). In patients taking statins, changes in CRP levels were not associated with changes in LDL-C (r=-0.02, p=0.87), but with baseline CRP levels (r=-0.38, p=0.000). CONCLUSION: Ezetimibe failed to reduce CRP levels in hypercholesterolemic patients taking statins despite significant reduction of LDL-C. This finding suggests that the anti-inflammatory effect of statin may not be secondary to cholesterol reduction, but via other mechanisms.
Azetidines ; C-Reactive Protein ; Cholesterol ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Lipoproteins ; Ezetimibe

Polytopic transmembrane protein, Niemann-Pick C1-Like 1 (NPC1L1) is localized at the apical membrane of enterocytes and the canalicular membrane of hepatocytes. It mediates intestinal cholesterol absorption and prevents extensive loss of cholesterol by transporting biliary cholesterol into hepatocytes. NPC1L1 is a molecular target of ezetimibe, an agent for hypercholesterolemia. Recently, NPC1L1 inhibition has been shown to prevent metabolic disorders such as fatty liver disease, obesity, diabetes, and atherosclerosis. In this review, the identification and characterization of NPC1L1, NPC1L1-dependent cholesterol transport, the relationship with pathogenesis of metabolic disease and its newly introduced function for virus entry are discussed.
Absorption ; Atherosclerosis ; Azetidines ; Cholesterol ; Enterocytes ; Fatty Liver ; Hepatocytes ; Hypercholesterolemia ; Intestines ; Membranes ; Metabolic Diseases ; Obesity ; Ezetimibe ; Virus Internalization

Familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular diseases, and is inherited as an autosomal dominant trait. The prevalence of heterozygous FH is one in five hundred people. Owing to dysfunctional low density lipoprotein (LDL) receptors due to genetic mutations, serum low density lipoprotein-cholesterol (LDL-C) levels are considerably increased from birth. FH is clinically diagnosed by confirmation of family history and characteristic findings such as tendon xanthoma or xanthelasma. Thus, clinical concern and suspicion are important for early diagnosis of the disease. Current guidelines recommend lowering LDL-C concentration to at least 50% from baseline. Statins are shown to lower LDL-C levels with high safety, and thus, have been the drug of choice. However, it is difficult to achieve an ideal level of LDL-C with a single statin therapy in the majority of FH patients. Alternatively, lipid lowering combination therapy with the recently-introduced ezetimibe has shown more encouraging results.
Azetidines ; Cardiovascular Diseases ; Early Diagnosis ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hyperlipoproteinemia Type II ; Lipoproteins ; Parturition ; Prevalence ; Tendons ; Xanthomatosis ; Ezetimibe

BACKGROUND AND OBJECTIVES: Although recent lipid-lowering therapies are effective in reducing low density lipoprotein-cholesterol (LDL-C) levels, many patients treated with lipid-lowering agents do not achieve target LDL-C levels, especially in very high risk patients. The aim of this study is to compare the effect of ezetimibe/simvastatin 10/20 mg and atorvastatin 20 mg on achieving a target LDL-C goal in very high risk patients. SUBJECTS AND METHODS: A total of 74 patients with very high risk were enrolled in the study. Very high risk patients were defined as patients that displayed established cardiovascular disease with multiple major risk factors, poorly controlled risk factors, multiple risk factors of the metabolic syndrome and acute coronary syndromes. Patients were randomized into two groups: ezetimibe/simvastatin 10/20 mg (n=36) and atorvastatin 20 mg (n=38). Follow-up lipid profile was obtained 6 weeks later. A target goal of LDL-C was defined as less than 70 mg/dL at follow-up. RESULTS: Baseline clinical and laboratory data were similar between the two groups. Achieving a target LDL-C goal was observed in 41.7% of Group 1 and 44.7% of Group 2 at 6 weeks (p=0.82). Changes in other lipid profiles were not significantly different but the tolerability of the two groups was similar. CONCLUSION: Ezetimibe/simvastatin 10/20 mg and atorvastatin 20 mg showed similar effects in achieving target LDL-C levels in patients with very high risk.
Acute Coronary Syndrome ; Azetidines ; Cardiovascular Diseases ; Follow-Up Studies ; Heptanoic Acids ; Humans ; Pyrroles ; Risk Factors ; Simvastatin ; Atorvastatin Calcium ; Ezetimibe

BACKGROUND/AIMS: Dyslipidemia is one of the major causes of cardiovascular disease in end-stage renal disease (ESRD) patients. Most of them are dyslipidemic despite the use of lipid-lowering agents. Ezetimibe is a novel chemical entity that inhibits the intestinal absorption of dietary and biliary cholesterol. This study evaluated the effects of ezetimibe on the lipid profile, inflammation markers, endothelial injury, and thrombogenesis in ESRD patients. METHODS: Sixty-five patients with serum low-density lipoprotein (LDL)-cholesterol levels > or =100 mg/d were recruited: 33 patients were on hemodialysis and 32 patients were on peritoneal dialysis. They were assigned randomly to the ezetimibe (10 mg) monotherapy group and the ezetimibe (10 mg) plus simvastatin (10 mg) combination therapy group. Both drugs were administered for 8 weeks. RESULTS: There were no significant differences in the baseline demographic and laboratory characteristics between the two groups. In the monotherapy group, the total and LDL-cholesterol levels were reduced by 14.7 and 21.9%, respectively. There were no changes in the high-density lipoprotein (HDL)-cholesterol or triglyceride levels. Fibrinogen increased significantly (p=0.04). In the combination therapy group, the total and LDL-cholesterol levels were reduced by 29.8 and 42.4%, respectively. There was an additional 15.1% reduction in total cholesterol and an additional 20.5% reduction in LDL cholesterol compared with monotherapy. Several patients complained of minor adverse effects and only one patient in the ezetimibe monotherapy group discontinued medication, because of diarrhea. CONCLUSIONS: In ESRD patients, ezetimibe used as combination therapy with a statin is more effective than ezetimibe monotherapy in ESRD patients.
Azetidines ; Cardiovascular Diseases ; Cholesterol ; Cholesterol, LDL ; Dyslipidemias ; Fibrinogen ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Inflammation ; Intestinal Absorption ; Kidney Failure, Chronic ; Lipoproteins ; Peritoneal Dialysis ; Renal Dialysis ; Simvastatin ; Ezetimibe

The polytopic transmembrane protein, Niemann-Pick type C1 Like 1 (NPC1L1), is the key point of exogenous cholesterol absorption and plays an important role in cholesterol metabolism. However, the molecular mechanism of NPC1L1's role in cholesterol uptake remains unclear. NPC1L1 expression is highly regulated by a variety of molecular actors. Nuclear receptors regulate NPC1L1 expression through its promoter region. Polyunsaturated fatty acids down-regulates NPC1L1 expression by the way of sterol regulatory element binding protein 2 (SREBP2). In addition, curcumin and sphingosine-phosphate take part in the regulation of NPC1L1 expression. NPC1L1 has been recognized as an essential protein for sterol absorption and is the molecular target of ezetimibe. Moreover, inhibition of the expression of NPC1L1 has been shown to have beneficial effects on components of the metabolic syndrome. The recent progress in the structure, function and regulation of NPC1L1 is reviewed.
Azetidines ; pharmacology ; Biological Transport ; Cholesterol ; metabolism ; Ezetimibe ; Fatty Acids ; metabolism ; Humans ; Membrane Proteins ; metabolism ; Metabolic Syndrome ; physiopathology ; Receptors, Cytoplasmic and Nuclear ; metabolism ; Sterol Regulatory Element Binding Protein 2 ; metabolism

BACKGROUND: Epicardial fat is a visceral thoracic fat and known to be related with presence of dyslipidemia and coronary arterial stenosis. We evaluated the effects and differences of statins on epicardial fat thickness (EFT) in patients underwent successful percutaneous coronary intervention (PCI). METHODS: In this retrospective cohort study, we enrolled consecutive patients underwent successful PCI and scheduled six to eight-months follow-up coronary angiography from March 2007 to June 2009. EFT was measured by echocardiography twice at the time of PCI and the follow-up coronary angiography. We included 145 patients (58 females; mean, 63.5 +/- 9.5 years). RESULTS: Of the 145 patients, 82 received 20 mg of atorvastatin (atorvastatin group) and 63 medicated with 10 mg of simvastatin with 10 mg of ezetimibe (simvastatin/ezetimibe group). With statin treatments, total cholesterol concentration (189.1 +/- 36.1 to 143.3 +/- 36.5 mg/dL, p < 0.001), triglycerides (143.5 +/- 65.5 to 124.9 +/- 63.1 mg/dL, p = 0.005), low density lipoprotein-cholesterol (117.4 +/- 32.5 to 76.8 +/- 30.9 mg/dL, p < 0.001) and EFT (4.08 +/- 1.37 to 3.76 +/- 1.29 mm, p < 0.001) were significantly decreased. Atorvastatin and simvastatin/ezetimibe showed similar improvements in the cholesterol profiles. However, atorvastatin decreased EFT more significantly than simvastatin/ezetimibe (EFT change 0.47 +/- 0.65 in the atorvastatin vs. 0.12 +/- 0.52 mm in the simvastatin/ezetimibe group; p = 0.001). CONCLUSION: In this study, the atorvastatin group showed significant reduction in EFT than in the simvastatin/ezetimibe group. This might be originated from the statin difference. More large, randomized study will be needed to evaluate this statin difference.
Azetidines ; Cholesterol ; Cohort Studies ; Constriction, Pathologic ; Coronary Angiography ; Coronary Stenosis ; Coronary Vessels ; Dyslipidemias ; Echocardiography ; Follow-Up Studies ; Heptanoic Acids ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Percutaneous Coronary Intervention ; Pyrroles ; Retrospective Studies ; Simvastatin ; Triglycerides ; Atorvastatin Calcium ; Ezetimibe

INTRODUCTIONWe aimed to assess the efficacy of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia.

METHODSA double-blind study was conducted to assess the effect of fixed dose combination of ezetimibe 10 mg plus atorvastatin 10 mg on lipid profile, oxidised low-density lipoprotein (ox-LDL), high-sensitivity C-reactive protein (hsCRP) and soluble intercellular cell adhesion molecule (sICAM) in dyslipidaemic patients with or at high risk of coronary artery disease, and compare it with atorvastatin 10 mg monotherapy. 30 patients were randomised to receive ezetimibe plus atorvastatin or atorvastatin once daily for four weeks.

RESULTSOf the 30 patients, 10 men and 5 women (mean age 54.3 ± 1.6 years) received ezetimibe plus atorvastatin, while 13 men and 2 women (mean age 53.7 ± 2.8 years) received only atorvastatin. The combination treatment significantly reduced total cholesterol (percentage treatment difference -14.4 ± 6.5, 95% confidence interval [CI] -1.0 to -27.7; p = 0.041) and LDL cholesterol (LDL-C; percentage treatment difference -19.9 ± 6.1, 95% CI -7.4 to -32.4; p = 0.003) compared to atorvastatin monotherapy. 13 patients on combination treament achieved the National Cholesterol Education Program target for LDL-C as compared to 9 patients on atorvastatin monotherapy (p = 0.032). Significant reductions in very low-density lipoprotein cholesterol, triglyceride, ox-LDL and sICAM were observed with combination treatment compared to atorvastatin monotherapy. However, no significant change was seen in high-density lipoprotein cholesterol or hsCRP levels between the two groups.

CONCLUSIONCombination treatment with atorvastatin and ezetimibe had relatively better lipid-lowering and anti-inflammatory efficacy than atorvastatin monotherapy.

Anti-Inflammatory Agents ; therapeutic use ; Anticholesteremic Agents ; administration & dosage ; Atorvastatin Calcium ; Azetidines ; administration & dosage ; C-Reactive Protein ; metabolism ; Double-Blind Method ; Drug Therapy, Combination ; methods ; Dyslipidemias ; drug therapy ; Ezetimibe ; Female ; Heptanoic Acids ; administration & dosage ; Humans ; Hypolipidemic Agents ; therapeutic use ; India ; Intercellular Adhesion Molecule-1 ; metabolism ; Lipoproteins, LDL ; metabolism ; Male ; Middle Aged ; Pyrroles ; administration & dosage ; Treatment Outcome

OBJECTIVEPatients with coronary artery disease (CAD, stenosis between 50% - 70% evidenced by coronary angiography) were treated with atorvastatin 40 mg (n = 19) or atorvastatin 10 mg in combination with ezetimibe 10 mg (n = 23). Blood lipid profile and metalloproteinases were monitored up to 3 months.

METHODSCholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), liver function, renal function, creatine kinase, MMP-2, MMP-9, TIMP-1 were measured at baseline and at 1 month and 3 months post therapy.

RESULTS(1) At 3 months, LDL-C was similarly reduced in monotherapy group [(1.94 +/- 0.49) mmol/L, 37.82% reduction compared to baseline] and in combined therapy group [(1.92 +/- 0.54) mmol/L, 38.26% reduction compared to baseline]. (2) AST, ALT, renal function and creatine kinase remained unchanged post various therapy (all P > 0.05). (3) MMP-2, MMP-9 significantly decreased and TIMP-1 significantly increased at 3 months compared to baseline in monotherapy group but these parameters remained unchanged in combined therapy group.

CONCLUSIONBoth therapy regimens were well tolerated and similarly effectively reduced blood lipids and 40 mg atorvastatin monotherapy regimen is superior to atorvastatin 10 mg plus ezetimibe 10 mg regimen in improving metalloproteinases parameters.

Adolescent ; Adult ; Aged ; Anticholesteremic Agents ; administration & dosage ; therapeutic use ; Atorvastatin Calcium ; Azetidines ; administration & dosage ; therapeutic use ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Coronary Artery Disease ; drug therapy ; metabolism ; Drug Therapy, Combination ; Ezetimibe ; Female ; Heptanoic Acids ; administration & dosage ; therapeutic use ; Humans ; Hypolipidemic Agents ; administration & dosage ; therapeutic use ; Male ; Metalloproteases ; blood ; Middle Aged ; Pyrroles ; administration & dosage ; therapeutic use ; Tissue Inhibitor of Metalloproteinase-1 ; blood ; Treatment Outcome ; Young Adult