Carotid Ultrasound Phenotypes Are Biologically Distinct

In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology , Santos et al1 report from a large Brazilian study (n=9792) that factors they analyzed explained a higher proportion of carotid intima-media thickness (IMT; ie, gave a higher R 2 in multiple regression) than reported in previous studies.See accompanying article on page 2054As pointed out by Inaba et al,2 it is crucial to distinguish between IMT measured according to the Mannheim consensus (in the far wall of the distal common carotid where there is no plaque) and methods that include plaque thickness in numerous locations, including the carotid bulb (the Atherosclerosis Risk in Communities [ARIC] and related protocols). IMT measured according to the Mannheim consensus does not represent atherosclerosis3; it is another phenotype. Studies that include plaque thickness in the measurement of IMT, and then analyze participants with and without plaque as if they were the same, confuse the issue by conflating the 2 kinds of IMT.Carotid ultrasound phenotypes are different: compensatory enlargement (positive remodeling) results in enlargement of the artery to accommodate plaque progression, without narrowing of the lumen.4 Thus, plaque burden represents the effects of oxidative stress and a lifetime’s exposure to coronary risk factors, whereas stenosis reflects factors that cause plaque rupture and thrombosis. An illustration of this principle is the differential relationship between Lp(a), a clotting factor,5 with carotid stenosis and occlusion, but not plaque burden.6Plaque thickness predicts cardiovascular risk.7 It is likely for that reason that the studies of IMT that include plaque thickness predicted cardiovascular risk,8 particularly in the elderly.9 In the ARIC study, the increment in risk above coronary risk factors gave an area under the curve of 0.08 with IMT, which increased to 0.17 with addition of the presence …