title: Carotid intima–media thickness: a suitable alternative for cardiovascular risk as outcome?
abstract: BACKGROUND
  Surrogate markers for cardiovascular disease might be of great value in observational research, clinical trials, and clinical practice. Carotid intima-media thickness (CIMT) is probably the most commonly used marker for atherosclerotic disease as an alternative for cardiovascular morbidity and mortality. A suitable marker for atherosclerosis, however, should meet several criteria before it can be validly used.
  
  
  RESULTS
  We reviewed the literature following a set of criteria for a surrogate marker. These include a comparison with a 'gold standard'; adequate reproducibility; cross-sectional relations with established risk factors and prevalent disease; relations with severity of atherosclerosis elsewhere in the arterial system; relations with the occurrence with future events; ability for a biomarker to change over time; ability to be affected by interventions over time; and relations between change over time in biomarker level and change in risk. A large number of studies from a variety of populations provide evidence for the validity of CIMT as a suitable measure of atherosclerotic disease. Data on the relation between change in CIMT and change in risk, however, is much sparser.
  
  
  CONCLUSIONS
  CIMT progression meets the criteria of a surrogate for cardiovascular disease endpoints and may be considered as a valid alternative for cardiovascular events as outcome. Further studies should examine the association between changes in CIMT and changes in risk for future events.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands. s.a.e.peters@umcutrecht.nl
authors.forename: Sanne A E
authors.initials: SA
authors.lastname: Peters
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Michiel L
authors.initials: ML
authors.lastname: Bots
mesh_terms: D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000209:etiology; D018450:Disease Progression; D006801:Humans; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging*; D017540:Tunica Media / Q000000981:diagnostic imaging*; D014463:Ultrasonography