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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.