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Technology Insight: ultrasound measurement of carotid plaque—patient management, genetic research, and therapy evaluation

Abstract

Various methods have been used to quantify atherosclerosis, beginning in the mid-1980s with ultrasound measurement of carotid intima–media thickness (IMT), and going on to coronary calcification assessed by electron-beam CT, measurement of carotid plaque by ultrasound, and measurement of carotid wall thickness by MRI. In recent years, it has become clear that carotid IMT, coronary calcification and carotid plaque reflect biologically and genetically different aspects of the atherosclerotic process, and will respond differentially to therapy. IMT represents mainly hypertensive medial hypertrophy; this measure is more predictive of stroke than of myocardial infarction, and is only weakly associated with traditional coronary risk factors. Carotid plaque area, on the other hand, is more strongly associated with traditional risk factors, and is more predictive of myocardial infarction than of stroke. A quantitative trait, called 'unexplained atherosclerosis', expresses the extent to which an individual has excess carotid plaque not explained by traditional risk factors, or the extent to which an individual is protected from traditional risk factors. Unexplained progression of plaque is an even more powerful tool for genetic research, because age, which accounts for the greatest proportion of baseline plaque, has much less influence on the rate of progression. Compared with IMT, measurement of carotid plaque volume by three-dimensional ultrasound reduces by two orders of magnitude the sample size and duration of treatment needed to evaluate new therapies. Measurement of carotid plaque is, therefore, an important tool for patient management, genetic research and evaluation of new therapies for stroke prevention.

Key Points

  • The burden of atherosclerosis can be measured as total carotid plaque area using two-dimensional ultrasound; this quantity is a strong predictor of cardiovascular outcomes

  • Patients in the top quartile of carotid plaque have 3.4 times the risk of stroke, death or myocardial infarction over 5 years compared with patients in the lowest quartile, after adjustment for age, sex, cholesterol, systolic blood pressure, smoking, diabetes, homocysteine, and treatment of lipids and blood pressure

  • Patients with plaque progression despite treatment of traditional risk factors have twice the risk, after adjustment for the same risk factors, as those with stable plaque or regression

  • Because plaque progresses along the carotid artery 2.4 times faster than it thickens, plaque area measurements are much more sensitive to effects of therapy than measuring thickness alone

  • Plaque is biologically and genetically distinct from intima–media thickness (IMT), stenosis and other phenotypes of atherosclerosis such as coronary calcium

  • Plaque area is more sensitive and specific for identifying patients free of coronary artery stenosis than are IMT or coronary calcium

  • Measurement of three-dimensional plaque volume reduces 100-fold compared with IMT, and 30-fold compared with MRI, the sample size and study duration required to study effects of new therapies for atherosclerosis

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Figure 1: Measurement of carotid plaque area using ultrasound.
Figure 2: Progression of total plaque area by age and sex.14
Figure 3: Disk segmentation method for measurement of plaque volume.
Figure 4: Plot depicting unexplained atherosclerosis.
Figure 5: Multiple regression analysis: baseline plaque area versus risk factors for atherosclerosis.

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Acknowledgements

I thank Maria DiCicco RVT for her original invention of plaque area measurement, and my colleagues Dr Aaron Fenster and Dr Robert Hegele for their invaluable collaboration in the development of 3D ultrasound methods for evaluating carotid plaque, and in genetic studies, respectively. The late Dr John Kreeft first suggested to me the multiple regression analysis for quantifying 'unexplained atherosclerosis'.

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Correspondence to J David Spence.

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Spence, J. Technology Insight: ultrasound measurement of carotid plaque—patient management, genetic research, and therapy evaluation. Nat Rev Neurol 2, 611–619 (2006). https://doi.org/10.1038/ncpneuro0324

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