title: Age, abdominal obesity, and baseline high-sensitivity C-reactive protein are associated with low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B responses to ezetimibe/simvastatin and atorvastatin in patients with metabolic syndrome.
abstract: BACKGROUND
  Treatment response to lipid-lowering therapy can vary in patients with the metabolic syndrome (MetS) due to various patient demographic and baseline characteristics.
  
  
  OBJECTIVE
  This study assessed the relationships between baseline characteristics and changes in lipid variables, high-sensitivity C-reactive protein (hs-CRP) and attainment of prespecified low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels in MetS patients treated with ezetimibe/simvastatin and atorvastatin.
  
  
  METHODS
  This is a post-hoc analysis of a multicenter, double-blind, randomized, 6-week parallel study in >1000 hypercholesterolemic subjects (median age of 59 years) with MetS and moderately high/high coronary heart disease risk who were treated with ezetimibe/simvastatin (10/20 and 10/40 mg) or atorvastatin (10, 20, 40 mg). Factors that could affect these treatments were assessed by multivariate analysis.
  
  
  RESULTS
  Increasing age, abdominal obesity (waist circumference ≥ 40/35 inches for men/women), and lower baseline hs-CRP were significant predictors of greater reductions in LDL-C, non-HDL-C, apolipoprotein B, total cholesterol, triglycerides, and very-low-density lipoprotein cholesterol but not for changes in HDL-C or apolipoprotein AI; effects of race and baseline triglycerides, non-HDL-C, LDL-C, or HDL-C levels were more limited. Age ≥ 65 years (versus <65 years) was also associated with significantly greater attainment of all LDL-C and non-HDL-C targets, whereas abdominal obesity, gender (female > male) and lower baseline LDL-C, non-HDL-C, triglycerides, and hs-CRP were associated with improved attainment for some of these targets. Blood pressure, fasting glucose, Homeostasis Model Assessment of Insulin Resistance tertiles, and diabetes did not predict response for any efficacy variable. Ezetimibe/simvastatin treatment (versus atorvastatin) was a significant predictor for change in most efficacy variables.
  
  
  CONCLUSIONS
  Treatment responses to ezetimibe/simvastatin and atorvastatin in at-risk patients with the MetS were related to age (≥ 65 years), abdominal obesity, and lower baseline hs-CRP. Ezetimibe/simvastatin treatment was found to be consistently more effective than atorvastatin at the specified dose comparisons across these subgroups. The clinical value of predictive factors requires further study in outcome trials.
authors.affiliation: Department of Epidemiology & Medicine,Prevention Intervention Center, College of Public Health, University of Iowa College of Public Health, 105 River Street, S455 CPBH, Iowa City, IA 52242, USA. jennifer-g-robinson@uiowa.edu
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Robinson
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.forename: Willa A
authors.initials: WA
authors.lastname: Hsueh
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Rosen
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lin
authors.forename: Arvind K
authors.initials: AK
authors.lastname: Shah
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Tomassini
authors.forename: Robert S
authors.initials: RS
authors.lastname: Lowe
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tershakovec
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001055:Apolipoproteins B / Q000097:blood; D000069059:Atorvastatin; D001384:Azetidines / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism*; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL / Q000097:blood*; D004311:Double-Blind Method; D000069438:Ezetimibe; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000097:blood / Q000503:physiopathology*; D011758:Pyrroles / Q000627:therapeutic use*; D019821:Simvastatin / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D001384:Azetidines; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D011758:Pyrroles; D002097:C-Reactive Protein; D000069059:Atorvastatin; D019821:Simvastatin; D000069438:Ezetimibe
keywords: Abdominal obesity; Age; Atorvastatin; Ezetimibe/simvastatin; LDL-C; Metabolic syndrome; Multivariate analysis; Non-HDL-C