Carotid intima-media thickness: a suitable alternative for cardiovascular risk as outcome?

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. Methods and 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. Conclusion: 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.