title: Mean common or mean maximum carotid intima-media thickness as primary outcome in lipid-modifying intervention studies.
abstract: OBJECTIVE
  Carotid intima-media thickness (CIMT) measurements are used as a disease outcome in randomized controlled trials that assess the effects of lipid-modifying treatment. It is unclear whether common CIMT or mean maximum CIMT should be used as the primary outcome. We directly compared both measurements using aspects that are of great importance in deciding which is most favorable for use in clinical trials.
  
  
  METHODS
  A literature search was performed (PUBMED, up to March 31, 2008). Fifteen trials with lipid-modifying treatment were identified that had information on both outcome measures. Common CIMT and mean maximum CIMT were compared on reproducibility, strength of relation with LDL and HDL cholesterol and congruency of their results (harm/neutral/beneficial) with data from event trials.
  
  
  RESULTS
  Findings showed that the reported reproducibility was high for both measurements, although a direct comparison was not possible. The relationship between the achieved LDL-C and HDL-C levels with CIMT progression was modest and showed no difference in magnitude between CIMT measurements. CIMT progression rates differed across carotid segments with the highest progression rates observed in the bifurcation segment. Treatment effects differed across carotid segments without a clear preference pattern. Trials using mean maximum CIMT progression more often (12 out of 15 studies) paralleled the findings of event trials in contrast to the mean common CIMT (11 out of 15 studies), a difference not reaching statistical significance.
  
  
  CONCLUSIONS
  Based on the literature, with equal results for reproducibility (assumed), lipid relationship and congruency with event findings, but with treatment effects that differ across carotid segments that can not be predicted, the mean maximum CIMT as the primary outcome may be preferred in trials on the impact of lipid-modifying interventions. One advantage is that information on mean common CIMT can generally be obtained easily in protocols assessing mean maximum CIMT, but not the other way around.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands.
authors.forename: Soner
authors.initials: S
authors.lastname: Dogan
authors.forename: Johannes Jacob Pieter
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Diederick Egbertus
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Michiel Leonardus
authors.initials: ML
authors.lastname: Bots
mesh_terms: D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000378:metabolism*; D059168:Carotid Intima-Media Thickness; D008076:Cholesterol, HDL / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D057847:Lipid Regulating Agents / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D012196:Review Literature as Topic
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D057847:Lipid Regulating Agents