Continuing Medical Education Course for "Use of Carotid Ultrasound to Identify Subclinical Vascular Disease and Evaluate Cardiovascular Disease Risk: A Consensus Statement for the American Society of Echocardiography Carotid Intima-Media Thickness Task Force" Accreditation Statement The American Society of Echocardiography is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The American Society of Echocardiography designates this educational activity for a maximum of 1 AMA PRA Category 1 Credits ™. Physicians should only claim credit commensurate with the extent of their participation in the activity. ARDMS and CCI recognize ASE's certificates and have agreed to honor the credit hours toward their registry requirements for sonographers. The American Society of Echocardiography is committed to resolving all conflict of interest issues, and its mandate is to retain only those speakers with financial interests that can be reconciled with the goals and educational integrity of the educational program. Disclosure of faculty and commercial support sponsor relationships, if any, have been indicated. Target Audience 1. Physicians, physicians' assistants, and nurses with an interest in cardiac and vascular imaging, preventive cardiology, and cardiovascular disease risk assessment. 2. Ultrasonographers with interest in vascular imaging and cardiovascular disease risk assessment. Objectives Upon completing this activity, participants will be able to: 1. Describe the rationale for using carotid ultrasound to identify subclinical vascular disease and to evaluate cardiovascular disease risk. 2. Explain the application of carotid ultrasound to cardiovascular disease risk assessment. 3. Describe the scanning technique for identifying subclinical vascular disease using carotid ultrasound. 4. Explain the key components of interpreting carotid ultrasound studies for cardiovascular disease risk assessment. Authors Disclosures James H. Stein, MD, FASE: Research grants: Siemens Medical Solutions, Sonosite Intellectual property: listed as the inventor of Patent #US 6,730,0235 "Ultrasonic Apparatus and Method for Providing Quantitative Indication of Risk of Coronary Heart Disease." It has been assigned to the Wisconsin Alumni Research Foundation. Emile R. Mohler III, MD: Speakers bureau for Merck, BMS-Sanofi and AstraZeneca; Research grant support from BMS-Sanofi, Pfizer and GSK. Christopher M. Rembold, MD: Advisory Board for Sonosite. Estimated Time to Complete This Activity: 1 hour

https://www.vasolabs.com/wp-content/uploads/2013/10/ASE-CIMT-consensus-paper.pdf

Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine.

Summary Cryptogenic (of unknown cause) ischaemic strokes are now thought to comprise about 25% of all ischaemic strokes. Advances in imaging techniques and improved understanding of stroke pathophysiology have prompted a reassessment of cryptogenic stroke. There is persuasive evidence that most cryptogenic strokes are thromboembolic. The thrombus is thought to originate from any of several well established potential embolic sources, including minor-risk or covert cardiac sources, veins via paradoxical embolism, and non-occlusive atherosclerotic plaques in the aortic arch, cervical, or cerebral arteries. Accordingly, we propose that embolic strokes of undetermined source are a therapeutically relevant entity, which are defined as a non-lacunar brain infarct without proximal arterial stenosis or cardioembolic sources, with a clear indication for anticoagulation. Because emboli consist mainly of thrombus, anticoagulants are likely to reduce recurrent brain ischaemia more effectively than are antiplatelet drugs. Randomised trials testing direct-acting oral anticoagulants for secondary prevention of embolic strokes of undetermined source are warranted.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(13)70310-7.pdf

Embolic strokes of undetermined source: the case for a new clinical construct

Context: The evidence that measurement of the common carotid intima-media thickness (CIMT) improves the risk scores in prediction of the absolute risk of cardiovascular events is inconsistent. Objective: To determine whether common CIMT has added value in 10-year risk prediction of first-time myocardial infarctions or strokes, above that of the Framingham Risk Score. Data Sources: Relevant studies were identified through literature searches of databases (PubMed from 1950 to June 2012 and EMBASE from 1980 to June 2012) and expert opinion. Study Selection: Studies were included if participants were drawn from the general population, common CIMT was measured at baseline, and individuals were followed up for first-time myocardial infarction or stroke. Data Extraction: Individual data were combined into 1 data set and an individual participant data meta-analysis was performed on individuals without existing cardiovascular disease. Results: We included 14 population-based cohorts contributing data for 45 828 individuals. During a median follow-up of 11 years, 4007 first-time myocardial infarctions or strokes occurred. We first refitted the risk factors of the Framingham Risk Score and then extended the model with common CIMT measurements to estimate the absolute 10-year risks to develop a first-time myocardial infarction or stroke in both models. The C statistic of both models was similar (0.757; 95% CI, 0.749-0.764; and 0.759; 95% CI, 0.752-0.766). The net reclassification improvement with the addition of common CIMT was small (0.8%; 95% CI, 0.1%-1.6%). In those at intermediate risk, the net reclassification improvement was 3.6% in all individuals (95% CI, 2.7%-4.6%) and no differences between men and women. Conclusion: The addition of common CIMT measurements to the Framingham Risk Score was associated with small improvement in 10-year risk prediction of first-time myocardial infarction or stroke, but this improvement is unlikely to be of clinical importance.

https://jamanetwork.com/journals/jama/articlepdf/1352111/joc120064_796_803.pdf

Common Carotid Intima-Media Thickness Measurements in Cardiovascular Risk Prediction A Meta-analysis

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

The endothelium, once considered a mere selectively permeable barrier between the bloodstream and the outer vascular wall, is now recognized to be a crucial homeostatic organ, fundamental for the regulation of the vascular tone and structure. Indeed, endothelial cells are able to synthesize and secrete a broad spectrum of anti-atherosclerotic substances, the most characterized of which is nitric oxide (NO), a gas that is generated from the metabolism of l-arginine by endothelial NO synthase (eNOS), constitutively expressed in endothelial cells (1). Under physiologic conditions, endothelial stimulation induces the production and release of NO, which diffuses to surrounding tissue and cells and exerts its cardiovascular protective role by relaxing media-smooth muscle cells, preventing leukocyte adhesion and migration into the arterial wall, muscle cell proliferation, platelet adhesion and aggregation, and adhesion molecule expression (1,2). In disease conditions, including the presence of cardiovascular risk factors, the endothelium undergoes functional and structural alterations, thus losing its protective role and becoming a proatherosclerotic structure (1). In the earliest stages, the principal endothelial alteration is merely functional and addressed as “endothelial dysfunction.” The fundamental feature of this condition is the impaired NO bioavailability. This can be the consequence of either a reduced production by eNOS or, more frequently, of an increased breakdown by reactive oxygen species (ROS) (1,2). In the presence of impaired NO bioavailability, the endothelium implements various physiological pathways in the attempt to compensate for NO deficiency. For instance, endothelium-dependent vasodilation is warranted, although impaired, also in the presence of cardiovascular risk factors by the production and release of endothelium-derived vasodilators other than NO, such as prostanoids and other endothelium-derived hyperpolarizing factors. Along with NO deficiency, a dysfunctioning endothelium also becomes the source of other substances and mediators that are detrimental to the arterial wall, including endothelin-1, tromboxane A …

https://care.diabetesjournals.org/content/diacare/32/suppl_2/S314.full.pdf

Endothelial Dysfunction as a Target for Prevention of Cardiovascular Disease

Background and Purpose— There is scant population-based evidence regarding extracranial carotid plaque surface irregularity and ischemic stroke. Using a prospective cohort design, we evaluated the association of carotid plaque surface irregularity and the risk of ischemic stroke in a multiethnic population. Methods— High-resolution B-mode ultrasound of the carotid arteries was performed in 1939 stroke-free subjects (mean age 69±10.0 years; 59% women; 53% Hispanic, 25% black, 22% white). Plaque was defined as a focal protrusion 50% greater than the surrounding area and localized along the extracranial carotid tree (internal carotid artery/bifurcation vs common carotid artery). Plaque surface was categorized as regular or irregular. Cox proportional hazard models were used to assess the association of surface characteristics and the risk of ischemic stroke. Results— Among 1939 total subjects, carotid plaque was visualized in 56.3% (1 plaque: 21.6%, >1 plaque: 34.7%, irregular plaque: 5.5%). During a mean fo...

Carotid Plaque Surface Irregularity Predicts Ischemic Stroke The Northern Manhattan Study

Arterial distensibility is a measure of the arterial ability to expand and contract with cardiac pulsation and relaxation.1 A decrease of arterial distensibility (increased artery wall stiffness) seems to be a common pathologic mechanism for many factors that lead to the occurrence and progression of the vascular changes associated with cardiovascular disease (CVD).2,3 Functional impairment of the arterial wall may occur in an early stage of the atherosclerotic process before structural wall changes become detectible as well as before the occurrence of clinical symptoms of CVD.3 Early detection of this impairment can lead to more effective strategies for the prevention of CVD. This concept that early changes in functional properties of the arterial wall precede the clinical stage of atherosclerosis has been investigated in peripheral arteries (femoral and brachial) and in the aorta for many years. Recent development of high-resolution and high-definition sonography has focused new investigations on the carotid arteries. With these techniques, arterial wall and vessel diameters can be assessed in a dynamic fashion through-out the cardiac cycle as the artery expands and contracts with each cardiac pulsation and relaxation.2,3 Arterial distensibility is, however, only an estimate of the mean strain and modulus at best because the entire soft tissue surrounding the vessel is responding to the change in the volume of the vessel, and the standard boundary identification methods of the vessel wall may not be as reliable as speckle-tracking methods.4

Carotid distensibility (CD) has been introduced as a novel risk factor for CVD in cross-sectional study designs from population-based cohorts, including Atherosclerosis Risk in Communities (ARIC), Second Manifestations of Arterial Disease (SMART), the Rotterdam Study, the Baltimore Longitudinal Study of Aging (BLSA), and the Multiethnic Study of Atherosclerosis (MESA).5–9 Nevertheless, the value of CD in predicting future stroke is currently under debate.10,11 The discrepancy over CD and its relationship to atherosclerosis seems to arise from several plausible factors, such as small sample sizes, different clinical characteristics of the study populations, analyses of CD restricted to different vascular beds, and measurement variability. Additionally, there is a lack of information regarding the reliability of CD measures. Therefore, we sought to evaluate the inter-reader reproducibility of the common carotid artery (CCA) diameters and distensibility measurements in a sample of 118 stroke-free subjects derived from a multiethnic population of northern Manhattan.

/pdf/carotid-artery-distensibility-a-reliability-study-3sd7bz85nw.pdf

Carotid artery distensibility: a reliability study.

Presence of calcified carotid plaque predicts vascular events: the Northern Manhattan Study.

Interleukin-2 levels are associated with carotid artery intima-media thickness.

Background
Impaired vascular function occurs early in atherogenesis. Brachial flow mediated dilatation (FMD) is a non-invasive measure of vascular function and may be an important marker of preclinical atherosclerosis. Data on the association between FMD and carotid plaque in multi-ethnic populations are limited. The objective of this study was to determine whether endothelial dysfunction is independently associated with carotid plaque in a community of northern Manhattan.

/pdf/endothelial-dysfunction-is-associated-with-carotid-plaque-a-3gucoetuix.pdf

Romel Ramas

Papers

Carotid Plaque Surface Irregularity Predicts Ischemic Stroke The Northern Manhattan Study

Carotid artery distensibility: a reliability study.

Presence of calcified carotid plaque predicts vascular events: the Northern Manhattan Study.

Interleukin-2 levels are associated with carotid artery intima-media thickness.

Endothelial dysfunction is associated with carotid plaque: a cross-sectional study from the population based Northern Manhattan Study.