Measurement of carotid plaque burden.

In light of the 2 recent decisions from US authorities regarding the use of carotid ultrasonography, it is timely to highlight the measurement of carotid plaque burden, as being distinct from assessment of severity of carotid stenosis or measurement of carotid intima-media thickness (IMT). The US Preventive Services Task Force recommended against screening for asymptomatic carotid stenosis, and the American Medical Association approved a category 1 reimbursement code for carotid IMT and plaque scanning. These seemingly contradictory decisions call for an explanation. Only approximately 2% of the population has asymptomatic carotid stenosis, and the vast majority of these patients (approximately 90%) would be better suited for intensive medical therapy than either carotid endarterectomy or carotid stenting. Screening the population to find patients for inappropriate intervention is therefore not a good idea. On the other hand, carotid imaging can identify high-risk patients who would benefit most from intensive medical therapy, so assessing preclinical atherosclerosis to find them makes sense. Treating patients to reduce their risk of cardiovascular events after they have been identified as already having cardiovascular disease leaves a large residual risk that could probably be diminished if preventive therapy, particularly lifestyle changes, was started earlier. Arguments for improved risk stratification using measurement of preclinical atherosclerosis were summarized in 2011 by Sillesen and Falk: “Most heart attacks and strokes occur in people at average risk-factor level who are misclassified by traditional risk factor scoring, as low or intermediate risk. ”1(p645) Measurement of IMT has been widely used for risk prediction in the past, but it is increasingly recognized that IMT adds very little to risk prediction based on risk factors, and progression of IMT does not predict cardiovascular events.2 An important emerging alternative to IMT measurement is measurement of carotid plaque burden, either as 2-dimensional total plaque area (TPA) or 3-dimensional plaque volume. Three-dimensional carotid plaque burden is highly correlated with coronary calcium scores, whereas IMT is not.3 Carotid imaging by ultrasonography has important advantages compared with coronary calcium measurement with regard to cost and avoidance of radiation. The TPA was shown in 2002 to be a strong predictor of cardiovascular events.4 After adjustment for age, sex, blood pressure level, cholesterol level, smoking, diabetes mellitus, homocysteine level, and treatment of elevated blood pressure and cholesterol levels, patients in the top quartile of TPA had a 5-year risk of stroke, death, or myocardial infarction that was 3.4 times higher than that of the first quartile. There was a stepped increase in risk; the adjusted 5-year risk of those events by quartile was 5.6% in the first quartile, 10.7% in the second quartile, 13.9% in the third quartile, and 19.5% in the top quartile. Patients in the top quartile of plaque area (>119 mm2) were at very high risk, approaching a 40% ten-year risk of stroke, death, or myocardial infarction, which warranted intensive medical therapy. Furthermore, patients with plaque progression (approximately half the patients) had twice the risk of those with stable plaque or regression of plaque area. These findings were validated in a prospective population-based study with more than 6000 participants in Tromsø, Norway, followed up now for more than 11 years. Mathiesen and colleagues5 found that the risk of both myocardial infarction and stroke were more strongly predicted by TPA than by IMT. A meta-analysis6 confirmed the superiority of TPA compared with IMT in cardiovascular risk prediction. Besides risk stratification, measurement of plaque burden is useful for genetic research. By saving residual scores in multiple regression (essentially, the distance off the regression line expressed in standard deviations), a quantitative trait is obtained that expresses the extent to which patients have more plaque or less plaque than would be predicted from risk factors. Extreme outliers can be identified; this approach reduces by three-fourths the sample size needed for genomewide association studies.7 Compared with IMT, measurement of carotid 3-dimensional plaque volume markedly reduces the sample size and duration of studies of new therapies for atherosclerosis (from 300 patients per group followed up for 2 years to 50 patients per group followed up for 6 months). The reason is that IMT changes only in thickness, whereas plaque volume changes in 3 dimensions— thickness, length, and circumferential extent of plaque. Measurement of carotid plaque volume is also more sensitive to the effects of therapy than is coronary intravascular ultrasonography because coronary plaques usually extend for the entire length of the arterial segment being measured and extend all around the circumference of the artery; change with therapy thus reduces to the average change in thickness along the length of the segment. Measurement of plaque burden can also be used to manage patients’ conditions beyond risk stratification. Based on the observation that half the patients in the 2002 article described above4 had progression of plaque, and their risk was twice that of patients with stable plaque or regression, a new approach to cardiovascular prevention, treating arteries instead of targeting risk factors, was developed. This approach markedly reduced risk among patients with asymptomatic carotid stenosis; after implementation of this approach, the 2-year risk of stroke declined from 8.8% to 1% and the risk of myocardial infarction dropped from 7.6% to 1%. 8 “Treating arteries” cannot be done with IMT measurement because the annual change in IMT is only 0.15 mm VIEWPOINT