This study sought to determine whether there is a segment specific effect between carotid artery wall thickness (IMT) measurements and cardiovascular risk factors. Our results indicate that, overall, mean of the maximum IMT in the common carotid artery is more strongly associated with cardiovascular risk factors than IMT measurements made in the carotid artery bulb or internal carotid artery.
We have found stronger associations for blood pressure in the common carotid artery than for other segments. This association was seen when systolic and diastolic pressure where both included in the models. We believe that the negative association with diastolic blood pressure is due to the effects of pulse pressure. When systolic and diastolic pressures are entered into separate models, both have positive associations with IMT. The bulb and ICA IMT have qualitatively stronger associations with cholesterol than those the CCA. Smoking and diabetes have stronger associations with the carotid bulb IMT than the CCA.
Differences in the strength of the association between IMT measurements in the different carotid artery segments and cardiovascular risk factors were described by O’Leary et al.2
in a two segment protocol. Similar to our findings, associations with blood pressure were stronger for CCA IMT than for Bulb/ICA IMT while the reverse was true for smoking status in adults aged 65 years or more2
. No comment was made on a differential effect of diabetes. Our findings might reflect a high prevalence of type 1 diabetics given the age distribution of our cohort. Our findings, while similar, show other qualitative differences. O’Leary et al. showed that 18% of the common carotid IMT and 17% of the proximal internal carotid IMT variability could be explained by cardiovascular risk factors. Our results show that 27% of the common carotid artery variability can be explained by cardiovascular risk factors. This decreases in the carotid artery bulb, were 11% of the variability can be explained and lower than the 17% reported by O’Leary et al. 2
. In our study, we also imaged at a higher level above the carotid artery bifurcation. We found that 8% of the variability of IMT in this segment was explained by traditional cardiovascular risk factors. Our image acquisition protocol resembles the ones used in the Atherosclerosis Risk in Communities (ARIC) study 18
and of the Rotterdam study12
. Data from ARIC have shown that strong correlations exist between IMT measurements in the different segments of the carotid artery 11
. However, segment specific differences in the associations of IMT with risk factors have been poorly studied with the exception of the association between age and IMT19
. We were able to obtain IMT measurements in a much greater proportion of the carotid artery segments than was done in ARIC or in the Rotterdam study. In the Rotterdam study, although common carotid artery IMT data were available in 96% of individuals, only 64% were available for the Bulb and 31% for the internal carotid artery12
. In ARIC, common carotid IMT was measurable in 79% of individuals in the CCA, 59% for the carotid bulb and 41% for the internal carotid artery19
. We believe that the level of completeness of our IMT data helped unmask segment specific differences in the association between IMT and risk factors.
An explanation for the differences in the association between risk factors and IMT measured in different segments is likely linked to bifurcation geometry and differences in hemodynamics. As discussed by Malek et al, shear-stress and shear rates near the lumen the common carotid artery and the widened carotid artery bulb14
. In the common carotid artery, blood pressure and shear-stress and shear-rates are strongly associated with carotid IMT, especially when no plaque is present 20, 21
. The carotid bifurcation has a more complex oscillatory low shear-stress that promotes the primary deposition of LDL cholesterol in the wall13, 14
. These processes ultimately affect the cellular constituent of the artery wall. A preponderance of foam cells is observed in the common carotid artery wall while more complex plaques are seen at the bifurcation15
. The segmental differences in the associations between risk factors and IMT are likely secondary to these basic pathophysiological differences. The complex interactions between blood pressure, blood flow and cholesterol deposition in the arterial wall make it difficult to isolate individual contributions based only on cross-sectional associations.
A limitation of our study is the relatively young age of our cohort given that the prevalence of cardiac and vascular disease increases in older individuals. Although this would seem to be a major limitation, pathological studies of young subjects dying non-cardiac associated events in the PDAY study (Pathological Determinants of Atherosclerosis in Youth) have confirmed the high prevalence of subclinical disease22
. A recent comparison between our cohort and this large autopsy study has shown similar associations in risk factor distributions23
Other authors have investigated possible differences in the associations between cardiovascular disease and IMT in the different carotid artery segments. Espeland et al. showed differences in the strength of the associations of IMT in the three carotid segments with age, hypertension, body-mass index in women and coronary-artery disease status10
. We also noted associations with BMI in both the common carotid artery and the internal carotid artery and qualitative differences in the associations of segment based IMT measurements with blood pressure and race. Tell et al. 24
noted, as we do, that age, hypertension and cigarette-smoking were similarly associated with all segments and that differences were seen for gender and diabetes. We also observed significant associations between diabetes and IMT in the common carotid and carotid artery bulb while fasting glucose levels were associated only with the common carotid IMT. However, in the study by Tell et al., the breakdown of carotid artery levels did not conform to the three segments of the carotid artery that we evaluated24
. Schott et al indicated in their study that risk factors might differentially affect IMT in the CCA, Bulb and ICA25
. In our multivariable models systolic blood pressure showed stronger associations with CCA IMT and bulb IMT while smoking was qualitatively stronger for the Bulb IMT. Contrary to our own results, these authors did not show a positive association between age and either ICA IMT and Bulb IMT25
Site specific differences in the associations between risk factors and IMT have also been seen in protocols that look at CCA IMT compared to wall thickness measurements that combine levels in the Bulb and the ICA26, 27
. In the EVA study, carotid plaques were defined as bulb/ICA IMT of > 2mm27
. Diabetes and current smoking were significantly associated with CCA IMT and not plaques (a rough equivalent of Bulb and ICA IMT). The strength of the association might have been lost due to the use of plaque as a dichotomized measure of Bulb/ICA IMT rather than a continuous measure of IMT as we did. There were strong associations between plaques and cholesterol levels. For LDL-c, we also observed a qualitative increase in the strength of the associations between LDL-c and IMT from the CCA to the ICA. Contrary to our study, the San Antonio study showed that in Hispanics, smoking was associated with ICA IMT and not CCA IMT, total cholesterol was more strongly associated with CCA IMT than for ICA IMT26
. We also note a qualitatively stronger association between Bulb IMT and smoking than for the CCA or ICA. The observation for LDL-c is opposite to the one we observe. As in our study, blood pressure was more strongly associated with CCA IMT than with ICA IMT26
. Data completeness in the San Antonio study was similar to that of our study.
Our study, as well as others, suggests that segment specific differences exist in the associations between cardiovascular risk factors and IMT. These differences might also translate into differences in clinical outcomes28, 29
. At this stage of the CARDIA study, the incident number of cardiovascular events is still too low for such an evaluation.
Carotid IMT is viewed as a potential tool for evaluating overall cardiovascular risk. Based on our data, recommendations to adopt only common carotid IMT as a marker of subclinical disease and of cardiovascular risk30, 31
might be justified since the other carotid segments have slight differences in their associations with cardiovascular risk factors. In addition, common carotid IMT has qualitatively stronger associations with well recognized risk factors that are associated with cardiovascular disease: age, gender and race.
We conclude that carotid IMT measurements made in the common carotid artery, carotid artery bulb and internal carotid artery are all associated with cardiovascular risk factors. While some cardiovascular risk factors show qualitatively stronger associations with IMT measured in the bulb or internal carotid artery, the common carotid artery IMT best reflects overall exposure to traditional cardiovascular risk factors.