The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: Endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society.

Carotid intima-media thickness (CIMT) has been shown to predict cardiovascular (CV) risk in multiple large studies. Careful evaluation of CIMT studies reveals discrepancies in the comprehensiveness with which CIMT is assessed-the number of carotid segments evaluated (common carotid artery [CCA], internal carotid artery [ICA], or the carotid bulb), the type of measurements made (mean or maximum of single measurements, mean of the mean, or mean of the maximum for multiple measurements), the number of imaging angles used, whether plaques were included in the intima-media thickness (IMT) measurement, the report of adjusted or unadjusted models, risk association versus risk prediction, and the arbitrary cutoff points for CIMT and for plaque to predict risk. Measuring the far wall of the CCA was shown to be the least variable method for assessing IMT. However, meta-analyses suggest that CCA-IMT alone only minimally improves predictive power beyond traditional risk factors, whereas inclusion of the carotid bulb and ICA-IMT improves prediction of both cardiac risk and stroke risk. Carotid plaque appears to be a more powerful predictor of CV risk compared with CIMT alone. Quantitative measures of plaques such as plaque number, plaque thickness, plaque area, and 3-dimensional assessment of plaque volume appear to be progressively more sensitive in predicting CV risk than mere assessment of plaque presence. Limited data show that plaque characteristics including plaque vascularity may improve CV disease risk stratification further. IMT measurement at the CCA, carotid bulb, and ICA that allows inclusion of plaque in the IMT measurement or CCA-IMT measurement along with plaque assessment in all carotid segments is emerging as the focus of carotid artery ultrasound imaging for CV risk prediction.

Carotid intima-media thickness and plaque in cardiovascular risk assessment

Background: Carotid atherosclerosis is a known biomarker associated with future vascular disease. The risk associated with small, nonstenotic carotid plaques is less clear. The objective of this study was to examine the association between maximum carotid plaque thickness and risk of vascular events in an urban multiethnic cohort. Methods: As part of the population-based Northern Manhattan Study, carotid plaque was analyzed among 2,189 subjects. Maximum carotid plaque thickness was evaluated at the cutoff level of 1.9 mm, a prespecified value of the 75th percentile of the plaque thickness distribution. The primary outcome measure was combined vascular events (ischemic stroke, myocardial infarction, or vascular death). Results: Carotid plaque was present in 1,263 (58%) subjects. After a mean follow-up of 6.9 years, vascular events occurred among 319 subjects; 121 had fatal or nonfatal ischemic stroke, 118 had fatal or nonfatal myocardial infarction, and 166 died of vascular causes. Subjects with maximum carotid plaque thickness greater than 1.9 mm had a 2.8-fold increased risk of combined vascular events in comparison to the subjects without carotid plaque (hazard ratio, 2.80; 95% CI, 2.04–3.84). In fully adjusted models, this association was significant only among Hispanics. Approximately 44% of the low-risk individuals by Framingham risk score had a 10-year vascular risk of 18.3% if having carotid plaque. Conclusions: Maximum carotid plaque thickness is a simple and noninvasive marker of subclinical atherosclerosis associated with increased risk of vascular outcomes in a multiethnic cohort. Maximum carotid plaque thickness may be a simple and nonexpensive tool to assist with vascular risk stratification in preventive strategies and a surrogate endpoint in clinical trials.

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Carotid plaque, a subclinical precursor of vascular events The Northern Manhattan Study

Carotid ultrasound provides quantitative measurements of carotid intima-media thickness (CIMT) that can be used to assess cardiovascular disease (CVD) risk in individuals and monitor ongoing disease progression and regression in clinical trials. It is non-invasive, rapid, reproducible, and carries no risk. Numerous epidemiological studies have established that CIMT is a marker of subclinical atherosclerosis and is associated with established CVD risk factors and with both prevalent and incident CVD. The use of CIMT in outcome trials as a surrogate or predictor of CVD outcomes is widespread. Carotid ultrasound is being employed to test the efficacy of CVD treatment in order to identify potential useful drugs earlier and to possibly speed regulatory approval. Successive trials have generated lessons learned and applied, with slow but steady improvement in CIMT measurement reproducibility.

/pdf/imaging-of-atherosclerosis-carotid-intima-media-thickness-1qars6ga1r.pdf

Imaging of atherosclerosis: carotid intima–media thickness

http://www.dei.unipd.it/~enrigri/Public/Sartori/molinari10b.pdf

Review: A state of the art review on intima-media thickness (IMT) measurement and wall segmentation techniques for carotid ultrasound

Background and Purpose— New therapies are being developed that are antiatherosclerotic but that lack intermediate end points, such as changes in plasma lipids, which can be measured to test efficacy. To study such treatments, it will be necessary to directly measure changes in atherosclerosis. The study was designed to determine sample sizes needed to detect effects of treatment using 3D ultrasound (US) measurement of carotid plaque. Methods— In 38 patients with carotid stenosis >60%, age±SD 69.42±7.87 years, 15 female, randomly assigned in a double-blind fashion to 80 mg atorvastatin daily (n=17) versus placebo (n=21), we measured 3D plaque volume at baseline and after 3 months by disc segmentation of voxels representing carotid artery plaque, after 3D reconstruction of parallel transverse duplex US scans into volumetric 3D data sets. Results— There were no significant differences in baseline risk factors. The rate of progression was 16.81±74.10 mm3 in patients taking placebo versus regression of −90.25±...

https://www.ahajournals.org/doi/pdf/10.1161/01.str.0000178543.19433.20

3D Ultrasound Measurement of Change in Carotid Plaque Volume A Tool for Rapid Evaluation of New Therapies

We investigated the utility of three manual planimetric methods to quantify carotid plaque volume. A single observer measured 15 individual plaques from 15 three-dimensional (3D) ultrasound (3D US)images of patients ten times each using three different planimetric approaches. Individual plaque volumes were measured (range: 32.6 – 597.1 mm 3 ) using a standard planimetric approach (M1) whereby a plaque end was identified and sequential contours were measured. The same plaques were measured using a second approach (M2), whereby plaque ends were first identified and the 3D USimage of the plaque was then subdivided into equal intervals. A third method (M3) was used to measure total plaque burden (range: 165.1 – 1080.0 mm 3 ) in a region ( ± 1.5 cm ) relative to the carotid bifurcation. M1 systematically underestimated individual plaque volume compared to M2 ( V 2 = V 1 + 14.0 mm 3 , r = 0.99 , p = 0.006 ) due to a difference in the mean plaque length measured. Coefficients of variance (CV) for M1 and M2 decrease with increasing plaque volume, with M2 results less than M1. Root mean square difference between experimental and theoretical CV for M2 was 3.2%. The standard deviation in the identification of the transverse location of the carotid bifurcation was 0.56 mm . CVs for plaque burden measured using M3 ranged from 1.2% to 7.6% and were less than CVs determined for individual plaque volumes of the same volume. The utility of M3 was demonstrated by measuring carotid plaque burden and volume change over a period of 3 months in three patients. In conclusion, M2 was determined to be a more superior measurement technique than M1 to measure individual plaque volume. Furthermore, we demonstrated the utility of M3 to quantify regional plaque burden and to quantify change in plaque volume.

Craig D. Ainsworth

Papers

3D Ultrasound Measurement of Change in Carotid Plaque Volume A Tool for Rapid Evaluation of New Therapies

Manual planimetric measurement of carotid plaque volume using three-dimensional ultrasound imaging.