Observational Studies

It is generally recognized that far-wall CIMT most accurately reflects the true thickness of the carotid wall, whereas the near wall is only an approximation of the true thickness. To the best of our knowledge, there is no published evidence showing that combined near-wall and far-wall common CIMT is superior to far-wall common CIMT alone with respect to prevalent or incident disease. This is because it has not been studied or has not been reported, or the studies that have addressed the issue were not a priori powered to detect differences in the magnitude of these relations. Yet near-wall CIMT measurements are as feasible and as reproducible as far-wall CIMT measurements. From experience, we know that there are individuals with thin far-wall common CIMT but with increased thickness at the near wall. Thus, near-wall measurement may still carry valuable information that would be missed when relying on the far wall alone.

Intervention Studies

There is evidence on the superiority of combined near-wall and far-wall CIMT compared with far-wall common CIMT alone. This evidence comes from trials in which both CIMT measurements were obtained. Trials evaluating the effect of lipid lowering on CIMT progression have shown that CIMT measurements of both the near and far walls are superior to trials in which only far-wall measurements were performed. This superiority could be explained by the reduction in random measurement error and the subsequent improvement in precision after combining of the near-wall and far-wall measurements.

Observational Studies

We agree with Polak that completeness rates for multiple angles of the common carotid artery across studies seem to depend on technical factors rather than on the use of multiple-angle protocols. As such, comparisons of completeness rates between studies are useless, because many factors in addition to the extensiveness of the ultrasound protocol alone may explain these rates. It is currently unknown whether CIMT measurements from multiple angles lead to differences in the magnitude of the relation with cardiovascular events compared with CIMT measurements from a single angle, because there are no published reports on that issue, or studies may lack power. We believe that a meta-analysis of individual participant data from existing cohort studies (i.e., the original data) would be well suited to address this issue in the future.

Intervention Studies

When the interest is in assessment of the rate of change and the effects of an intervention, few studies have been published that addressed the issue of multiple-angle approaches and treatment effects directly. These studies showed that extensive ultrasound protocols, including near-wall and far-wall measurements from two or more angles, provide a better balance among high reproducibility, large progression rates, and large and precise intervention effects compared with single-angle protocols from the far wall alone. This may especially be beneficial in settings in which sample sizes and effect sizes are small.

Observational Studies

We agree with Polak that completeness rates for multiple angles of the common carotid artery across studies seem to depend on technical factors rather than on the use of multiple-angle protocols. As such, comparisons of completeness rates between studies are useless, because many factors in addition to the extensiveness of the ultrasound protocol alone may explain these rates. It is currently unknown whether CIMT measurements from multiple angles lead to differences in the magnitude of the relation with cardiovascular events compared with CIMT measurements from a single angle, because there are no published reports on that issue, or studies may lack power. We believe that a meta-analysis of individual participant data from existing cohort studies (i.e., the original data) would be well suited to address this issue in the future.

Intervention Studies

When the interest is in assessment of the rate of change and the effects of an intervention, few studies have been published that addressed the issue of multiple-angle approaches and treatment effects directly. These studies showed that extensive ultrasound protocols, including near-wall and far-wall measurements from two or more angles, provide a better balance among high reproducibility, large progression rates, and large and precise intervention effects compared with single-angle protocols from the far wall alone. This may especially be beneficial in settings in which sample sizes and effect sizes are small.

Observational Studies

There is no published evidence to show that CIMT measurements from the carotid bifurcation and internal carotid artery are superior to the common carotid artery when evaluating the relation between CIMT and incident cardiovascular disease. Several studies have shown an increased magnitude of the relation of a multiple-segment CIMT with future events compared with common CIMT alone, yet these studies were never powered to address this issue, and the differences were therefore never statistically significant.

Intervention Studies

With respect to intervention studies, there are trials showing a beneficial response of intervention on the rate of change in CIMT assessed using a single-angle far-wall common CIMT measurement. However, the statement by Polak that one view of the common carotid artery is sufficient seems to be incorrect, as there are also examples of trials in which such an approach would have failed. Yet comparisons between studies will never provide conclusive answers, because it remains unknown whether trials showing effects on the common carotid artery alone would have found similar or improved effects had an extensive protocol been used. Instead, one must look at differences within trials that measured across multiple carotid segments. Indeed, and in contrast to Polak’s point of view, there are trials that failed to find an intervention effect on common CIMT, whereas a beneficial effect was found on the aggregate CIMT measure and on clinical events. Also, we recently performed detailed within-study evaluations of the best ultrasound protocol in terms of the selection of carotid segments and found mixed results. Measuring the near and far wall of the common carotid artery at multiple angles alone was superior to also measuring the carotid bifurcation and internal carotid artery in healthy individuals and in patients with familial hypercholesterolemia, whereas the three-segment approach was superior to the common carotid artery approach alone in individuals with mixed dyslipidemia and asymptomatic subclinical atherosclerosis.

These findings underscore our viewpoint that an ideal ultrasound protocol does not exist and that the choice of an ultrasound protocol should always depend on a well-considered evaluation of the expected rates of change and associated precision at the different carotid segments. However, because it remains impossible to predict at which carotid segment drug therapies will have their effect, extensive protocols may be preferred.