title: Effects of ezetimibe on markers of synthesis and absorption of cholesterol in high-risk patients with elevated C-reactive protein.
abstract: OBJECTIVE
  High-risk subjects with elevated C-reactive protein (CRP) are at high risk for cardiovascular events and frequently require potent statins or combined lipid-lowering therapy to achieve lipid targets and decrease inflammation. Our study aimed at evaluating the effects of three lipid-modifying therapies on LDL-cholesterol, CRP levels and markers of cholesterol absorption and synthesis.
  
  
  METHODS
  A prospective intervention study was performed in high cardiovascular risk individuals receiving atorvastatin 10mg daily for four weeks. Those with CRP≥2.0mg/L were randomized to another four-week treatment period with atorvastatin 40mg, ezetimibe 10mg or the combination of atorvastatin 40mg / ezetimibe 10mg. Lipids, markers of cholesterol absorption (campesterol and β-sitosterol), and synthesis (desmosterol), as well as CRP were quantified at baseline and end of study.
  
  
  RESULTS
  One hundred and twenty two individuals were included. Atorvastatin alone or combined with ezetimibe reduced both LDL-cholesterol and CRP (P<0.002 vs. baseline; Wilcoxon); ezetimibe did not modify CRP. Ezetimibe-based therapies reduced absorption markers and their ratios to cholesterol (P<0.0001 vs. baseline, for all; Wilcoxon), whereas atorvastatin alone increased campesterol/cholesterol and β-sitosterol/cholesterol ratios (P<0.05 vs. baseline; Wilcoxon). In addition, ezetimibe also increased desmosterol and desmosterol/cholesterol ratio (P<0.0001 vs. baseline; Wilcoxon).
  
  
  CONCLUSIONS
  These results contribute to understanding the link between cellular cholesterol homeostasis, inflammation and lipid-modifying therapies. Our findings highlight the broader benefit of combined therapy with a potent statin and ezetimibe decreasing inflammation, and preventing increase in cholesterol biosynthesis, an effect not observed with ezetimibe alone.
authors.affiliation: Lipids, Atherosclerosis and Vascular Biology Section, Cardiology Division, Department of Medicine, Federal University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Simone P
authors.initials: SP
authors.lastname: Barbosa
authors.forename: Lívia C
authors.initials: LC
authors.lastname: Lins
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Fonseca
authors.forename: Lívia N
authors.initials: LN
authors.lastname: Matos
authors.forename: Ana C
authors.initials: AC
authors.lastname: Aguirre
authors.forename: Henrique T
authors.initials: HT
authors.lastname: Bianco
authors.forename: Jonatas B
authors.initials: JB
authors.lastname: Amaral
authors.forename: Carolina N
authors.initials: CN
authors.lastname: França
authors.forename: Jose M
authors.initials: JM
authors.lastname: Santana
authors.forename: Maria C
authors.initials: MC
authors.lastname: Izar
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D001384:Azetidines / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D002784:Cholesterol / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000378:metabolism*; D003897:Desmosterol / Q000378:metabolism; D000069438:Ezetimibe; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010840:Phytosterols / Q000378:metabolism; D011446:Prospective Studies; D011758:Pyrroles / Q000494:pharmacology*; D012307:Risk Factors; D012855:Sitosterols / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010840:Phytosterols; D011758:Pyrroles; D012855:Sitosterols; D003897:Desmosterol; C021273:campesterol; C025473:gamma-sitosterol; D002097:C-Reactive Protein; D002784:Cholesterol; D000069059:Atorvastatin; D000069438:Ezetimibe