Surrogate markers for cardiovascular disease: structural markers.

Abstract

Pignoli et al1 validated the concept that intima-media thickness (IMT), as measured by B-mode ultrasound and applied either in vitro or in situ at the time of autopsy, reflected direct measurements of aortic and/or carotid specimens. Values obtained by ultrasound at autopsy and by direct measurement were similar to those obtained from living subjects. The characteristic double-line pattern was most consistently found in the far wall of postmortem specimens judged to be relatively normal or affected only by fatty streaks. Histologically, these segments showed homogeneous intima with varying amounts of intimal thickening, intimal fibrosis, internal elastic lamina fragmentation, and duplication. In specimens with more advanced atherosclerosis, the double-line pattern was sometimes perturbed and more complex; these samples showed evidence of a fibrous/muscular cap with a lipid and/or necrotic core and, histologically, the intima showed focal areas of fibrotic smooth muscle cell proliferation, microcalcification, and necrosis. Based on this important article, it is clear that carotid IMT is a direct measure of the status of the vascular wall, and abnormalities are not a surrogate but a direct measure of atherosclerotic and arteriosclerotic processes. The issue of surrogacy pertains to whether a measurement in the carotid bed is associated with atherosclerosis in other beds, particularly the coronary bed and, even more important, whether this measurement is predictive of vascular events that result from atherothrombotic disease. ### Methodology Carotid ultrasound is routinely applied for evaluation of ischemic cerebrovascular signs (eg, bruits) and symptoms. In the context of risk stratification, however, the goal is to identify preclinical disease. The degree of carotid disease that appears to be of prognostic value is much subtler, requiring meticulous and detailed measurements of IMT through B-mode ultrasound. These measurements can be made in a reproducible and reliable fashion if sonographers and those making the measurements are trained comprehensively and …