We have found that the difference in common carotid artery IMT between ED and PS is on average 0.041 mm. The principal predictors of this difference are pulse pressure and ethnicity. We also have found that the associations of risk factors with ED-IMT and PS-IMT are similar. We also note that adoption of IMT measurements made at ED when compared to normative data based on PS-IMT might lead to an overestimation of 31.3% of individuals at high risk for cardiovascular disease.
Before this study, there had not been a systematic evaluation of how much the phase of the cardiac cycle changes the IMT measurement. In vitro studies had suggested that the artery wall was noncompressible.16–17
This implied, on the basis of conservation of mass and lack of longitudinal stretching, that the wall thickness and therefore IMT would decrease as the artery diameter increased during systole. Selzer et al4
showed that common carotid IMT was lower at PS than for ED by an average of 5.3% in 24 individuals. Devereux et al18
reported a 5.3% decrease in carotid IMT with high-resolution M-mode imaging. However, Baldassarre et al19
studied a small sample of 14 subjects and did not detect any systematic difference in IMT during the cardiac cycle.
We estimate the change in IMT during the cardiac cycle to be on average 0.041 mm. We also show for the first time that the difference between ED-IMT and PS-IMT is associated with pulse pressure and ethnicity but not with age, sex, or any other traditional cardiovascular risk factor. On the basis of these observations, the distending pressure on the artery wall is the principal contributor to the difference in IMT between systole and diastole. Ethnic differences are described for the first time and could represent inherent differences in the structure of the arterial wall.
Previous IMT studies have (1) underestimated the role of the cardiac cycle20
, (2) used the R wave to gate the IMT measurement to ED21
, or (3) used a visual evaluation of the smallest diameter to identify the ED frame.22
The carotid image used for IMT measurements often is selected after review of a cine buffer of images stored in the ultrasound device or after review of videotaped images. The image frame closest to ED typically is selected by review of the images and by picking the image in which the diameter of the artery appears the smallest. Our findings show marginal differences in the associations of risk factors with ED-IMT and PS-IMT measurements. The difference in the explained variability of the models is small, at 0.74%, and is unlikely to affect the associations between risk factors and IMT within a given study. However, if results of different IMT studies are to be combined, appropriate adjustments might be needed.
Strengths of our study include the multiethnic composition of the cohort, the use of a highly standardized IMT imaging protocol, and the use of a high-resolution ultrasound imaging device. In addition, the data were acquired from the far wall of the common carotid artery, a preferred site when consideration is being given to the use of IMT for cardiovascular risk assessment.8
Weaknesses include the possibility that associations between change in IMT and risk factors might have been underestimated because of the small magnitude of the change being assessed and the variability of the measurement process. We also are limited by the fact that only the right carotid artery was studied. However, IMT evaluations restricted to the right carotid are reproducible, have predictive power for outcomes, and also are useful for assessing the response to lipid-lowering therapies.21,23
We have shown that cardiovascular risk factors are associated with our IMT measurements, such that 20% of the variability in IMT can be accounted for. This is within the expected range reported in prior publications that included the right and left common carotid arteries. In these studies, cardiovascular risk factors accounted for up to 27% of IMT variability in middle-age individuals24
17% for individuals ≥65 years of age.25
This issue requires further clarification because derived IMT normative data are different for the right and left common carotid arteries.8
It is not clear whether the IMT values used for risk assessment should be derived from either the right or left common carotid arteries or whether an average of both values should be considered.
Asymptomatic individuals can be classified as being at high risk for cardiovascular disease if their IMT is above the 75th percentile.6–7
A panel of the American Heart Association and American College of Cardiology Foundation on cardiovascular risk in asymptomatic individuals gave a Class IIa recommendation for the use of carotid IMT for cardiovascular risk assessment6
and referenced a source of normative data.8–9
However, these source IMT data were measured on PS images.9
According to our data, use of these IMT normative data might classify patients inappropriately as being at high risk and increase their likelihood of undergoing further investigation or treatment when their IMT is measured at ED. Although it is clear that Atherosclerosis Risk in Communities (ARIC) IMT values acquired at PS26
have predictive power for cardiovascular events,27
the same is true for IMT measurements made at ED.28
We recognize that the magnitude of this effect is small given the inherent variability of IMT measurements, but the effect is a quantifiable one nonetheless. In addition, the differences in IMT between PS and ED are greater than those seen between men and women (, ). Because men and women have different sets of normative data, it would seem logical that IMT normative values should also include a correction for the phase of the cardiac cycle.
We conclude that IMT is slightly larger at ED than it is at PS in part because of pulse pressure. Our observations confirm the need to control for the phase of the cardiac cycle when change in IMT is measured over time. The magnitude of the difference in IMT during the cardiac cycle can affect risk stratification in asymptomatic individuals because of mismatch between acquisition protocol and IMT normative data.