Carotid Intima-Media Thickness and Plaque Imaging

The extent of carotid artery atherosclerosis is strongly related to the extent of coronary artery atherosclerosis. Carotid duplex ultrasound is used to evaluate for the presence and extent of occlusive, advanced, flow-limiting carotid artery atherosclerosis. Ultrasound imaging of carotid artery wall thickness is a distinctly different test that is used to assess CVD risk. The superficial location and easy accessibility of the common carotid artery permit accurate, reproducible ultrasound imaging. The walls of the carotid artery are composed of the lumen-intima interface and the media-adventitia interface that together produce two echogenic lines in the far wall of the carotid artery ( Fig. 30-1 ). Measurement of the combined thickness of these interfaces comprises the CIMT ( Fig. 30-2 ). The presence of subclinical arterial injury is demonstrated by increased CIMT, and the presence of carotid plaque represents subclinical atherosclerotic disease.

Longitudinal plane demonstrating “double-line sign” on near and far walls of the common carotid artery.

Leading edge–to–leading edge measurement of the far-wall common carotid artery CIMT.

Relationship between Carotid Intima-Media Thickness and Cardiovascular Disease Events

There are 11 published prospective, population-based studies of CIMT and CVD risk that included at least 1000 participants and presented odds ratios or relative risks adjusted for CVD risk factors ( Table 30-1 ). Many of these studies recently were reviewed in detail. These studies demonstrated that increased CIMT is associated with significantly increased risk for MI, stroke, and/or coronary heart disease death. Two additional large studies had similar findings. In several studies, the adjusted relative risks associated with the greatest degrees of wall thickness (see cut points in Table 30-1 ) were high enough (>2.0) that they would be expected to improve coronary heart disease risk prediction in appropriately selected patients. Furthermore, CIMT measurements improve on traditional risk factors for classification of patients in regard to the presence of significant angiographic coronary artery disease and risk of recurrent CVD events. In an analysis of unselected participants in the Atherosclerosis Risk in Communities (ARIC) study, CIMT values significantly (albeit modestly, ~0.02) increased the area under the receiver operator characteristic curve (AUC) for prediction of cardiovascular events in men. In the Multi-Ethnic Study of Atherosclerosis (MESA), increased CIMT was positively associated with CVD events and stroke. As in ARIC, CIMT values modestly increased the AUC (by ~0.01) for prediction of CVD compared with traditional risk factors alone.

The relationship between increasing CIMT and incident cardiovascular events has been established across a wide age range. However, the strongest data are for individuals between 42 and 74 years of age; several studies of individuals in this age range show similar results (see Table 30-1 ). For younger adults (18 to 42 years old), consistent, strong relationships between increasing risk factor burden and CIMT, as well as between CIMT and emerging risk factors, have been demonstrated. In the Carotid Atherosclerosis Progression Study (CAPS), CIMT predicted CVD events even among 2436 individuals <50 years old (mean, 38.7 years; standard deviation, 7.0 years). In that study, the relative risk associated with increased CIMT appeared to be higher among younger than older adults.

In the Tromsø Study of 6226 subjects, there were conflicting data regarding the predictive value of CIMT and CVD events. The CIMT in the common carotid artery did not demonstrate a statistically significant relationship between CIMT and first MI, but there was a significant relationship, in both men and women, when CIMT was evaluated with use of both the common carotid artery and bulb segments. However, this study measured CIMT only in the right carotid artery. The American Society of Echocardiography (ASE) Consensus Statement recommends that CIMT be evaluated with the far wall of both the right and left common carotid arteries, in conjunction with plaque imaging in the common carotid, bulb, and internal carotid artery segments, because atherosclerosis progresses more rapidly in the bulb and internal carotid artery segments, and the effects of risk factors on CIMT can vary by segment. This approach has been validated, and its predictive value has been rigorously demonstrated in other studies (see Table 30-1 ).

Relationship between Carotid Plaques And Cardiovascular Disease Events

Carotid plaque presence is associated with the presence of coronary artery plaque and the occurrence of future cardiovascular and cerebrovascular disease events. Most carotid plaques are found in the bulb and proximal internal carotid artery segments because of turbulent flow. Atherosclerosis and CIMT progress more rapidly in the bulb and internal carotid segments compared with the common carotid artery. Seven population-based studies that included at least 1000 participants and presented relative risks or hazard ratios adjusted for CVD risk factors have demonstrated the predictive power of carotid plaque ( Table 30-2 ). In these studies, the relative risks associated with the presence of plaque were similar to or slightly higher than those observed with increased CIMT. Two additional large studies of carotid plaque presence and two studies that evaluated plaque area had similar results. The presence of carotid plaque predicted future CVD events among young, middle, and elderly subjects. A prospective study of 367 elderly men (>70 years old) demonstrated that the presence of carotid plaque significantly improved the AUC for prediction of all-cause mortality and cardiovascular mortality, even after considering traditional cardiovascular risk factors and use of medications (by ~0.03 to 0.04). In San Daniele Township, the presence of carotid plaque or CIMT >1 mm had greater predictive value than the Framingham risk score for ischemic cerebrovascular disease events and a small increase in AUC (by ~0.01).

Unfortunately, the definition of carotid plaque in most reported studies was not uniform. Most studies identified plaque as focal widening relative to adjacent segments with protrusion into the lumen and/or had a minimum wall thickness. The Mannheim Carotid Intima-Media Thickness Consensus Report suggested that plaque should be defined as “a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT or demonstrates a thickness of ≥1.5 mm.” An ASE report defined nonobstructive plaque as “the presence of focal thickening at least 50% greater than that of the surrounding vessel wall.” These definitions are similar to those used in the ARIC study, the largest prospective cohort study that demonstrated the predictive value of plaque in cardiovascular risk assessment. The ASE Consensus Statement recommended that carotid plaque be defined as the presence of focal wall thickening that is at least 50% greater than that of the surrounding vessel wall or as a focal region with CIMT >1.5 mm that protrudes into the lumen and is distinct from the adjacent boundary.

Quantification of carotid plaque area also is a strong predictor of future CVD events. In some studies, the two-dimensional total carotid plaque area was more predictive of MI than CIMT, after adjustment for traditional CVD risk factors. In the Tromsø Study, baseline carotid plaque area was a stronger predictor of future MI than CIMT (see Tables 30-1 and 30-2 ), especially in women. In both men and women, there was a direct correlation between total plaque area and MI incidence. In a report of 1686 individuals in an atherosclerosis prevention clinic, those in the highest quartile of carotid plaque had the greatest risk of future vascular events (see Table 30-2 ), and subjects with progression of carotid plaque area doubled their risk of future events compared with subjects with stable plaque area.

The ASE does not currently recommend risk stratification based on carotid plaque measurements outside of the research setting because of their complex geometry and the absence of a published, widely applicable standard for imaging and measurement of carotid plaque area. Carotid plaque area and even volume have been used in limited clinical settings to assist with risk stratification and to evaluate the efficacy of atherosclerosis disease management. However, the incremental predictive value of the quantification of carotid plaque, beyond defining the presence of plaque, is unknown.

Guideline And Consensus Statement Recommendations For Carotid Intima-Media Thickness

The use of carotid ultrasound for evaluation of CIMT and carotid plaque as a clinical risk prediction tool has been addressed in several guidelines and consensus statements. In 2000, the American Heart Association Prevention Conference V concluded that CIMT “can now be considered for further clarification of coronary heart disease risk assessment at the request of a physician,” provided it is performed by an experienced laboratory. In 2001, the National Cholesterol Education Program Adult Treatment Panel III stated that CIMT “could be used as an adjunct in coronary heart disease risk assessment … the finding of an elevated carotid IMT (e.g., ≥75th percentile for age and sex) could elevate a person with multiple risk factors to a higher risk category.” This expert panel concluded that “if carried out under proper conditions, carotid IMT could be used to identify persons at higher risk than that revealed by the major risk factors alone.” In 2003, the 34th Bethesda Conference supported the use of CIMT as a screening test for subclinical vascular disease. The clinical application of CIMT methodology was reviewed and supported in 2006 in a report from the American Society of Echocardiography and the Society of Vascular Medicine and Biology. In 2007, the European Society of Cardiology described increased CIMT as a marker of hypertensive target organ damage. The most recent, comprehensive recommendations on the use of carotid ultrasound, including CIMT and carotid plaque presence, for cardiovascular risk assessment are contained in a Consensus Statement published in 2008 by the American Society of Echocardiography and were endorsed by the Society of Vascular Medicine.