Carotid Ultrasound Phenotypes Are Biologically Distinct.

1 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. As 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 atherosclerosis 3 ; 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. 6 Plaque 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 of plaque. However, meta-analyses found that IMT measured without plaque is a weak predictor of cardiovascular risk, 10 and progression of IMT did not predict cardiovascular risk 11 nor did regression of IMT. 12 A meta-analysis by Inaba et al 2 concluded that plaque area was a stronger predictor of risk than IMT. Adam and Bojara 13 also found, in a workplace health program study in >4000 participants, that plaque area and plaque type, but not IMT, predicted coronary stenosis and cardiovascular risk. A report from the Multi-Ethnic Study of Atherosclerosis (MESA) indicated that coronary calcium, but not IMT, predicted cardiovascular risk in the overall population. 14 Brook et al 15 reported that carotid total plaque area was more …