ABSTRACT
Table 1 provides a summary of observational studies that have identified the correlative relationship between plasma homocyst(e)ine level and carotid atherosclerosis as measured by duplex ultrasonography. The most common technique used for the measurement of carotid atherosclerosis has been quantification of intima-media thickness (IMT), usually defined as the distance between the characteristic echoes from the lumen-intima and media-adventitia interfaces (47). The IMT is well accepted as a reproducible, non-invasive measure of peripheral atherosclerosis, although its correlation with coronary artery disease is less convincing (48). Although the studies described in Table 1 are heterogeneous in experimental design, inclusion criteria, and population (ranging from Northern Europeans to Japanese), they document that homocyst(e)ine as a continuous analytical variable will correlate with increasing severity of carotid atherosclerosis. With the exception of one study published by Voutilainen et al. (44) that observed this effect only in men, the robust association between the severity of carotid atherosclerosis and homocyst(e)ine has no gender preference. Other notable exceptions among the studies listed in Table 1 are those conducted by Taylor et al. (49) and Fagerberg et al. (50), both of which found no relationship between homocyst(e)ine level and measurements of carotid atherosclerosis (49,50). In the former report, 169 patients with symptomatic peripheral arterial disease (claudication, rest pain, digital gangrene, or amputation) and/or cerebrovascular disease (ischemic stroke or transient ischemic attack) were dichotomized into two groups with ‘‘elevated’’ or normal levels of homocyst(e)ine and were evaluated by serial ultrasonography. There was no difference between the groups in progression of carotid atherosclerosis as defined by conversion of a patent to an occluded vessel or by advancement to a more severe compromise of the arterial lumen. However, worsening of the ankle-brachial index measuring arterial perfusion in the leg was observed selectively in the ‘‘elevated’’ homocyst(e)ine group. In the second study by Fagerberg et al. (50), 800 men with insulin sensitivity and of the same age (58 years) showed no association between measurements of common carotid artery IMT and plasma homocyst(e)ine levels that were controlled appropriately for vitamin B12 and folic acid levels.
