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Echocardiography (ASE) Carotid Intima-Media. Thickness ... the ASE consensus statement in detail and to pay particular ... tation, reporting, training, and certification.1 High- lights of ... of Medicine and the Bloomberg School of Public Health,.
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COMMENTARY

Use of Carotid Ultrasound to Identify Subclinical Vascular Disease and Evaluate Cardiovascular Disease Risk: Summary and Discussion of the American Society of Echocardiography Consensus Statement James H. Stein, MD;1 Claudia E. Korcarz, DVM, RDCS;1 Wendy S. Post, MD, MS2

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n February 2008, the American Society of Echocardiography (ASE) Carotid Intima-Media Thickness (CIMT) Task Force published its recommendations for the use of carotid ultrasonography to identify subclinical vascular disease to assist with the evaluation of cardiovascular disease (CVD) risk.1 This consensus statement was endorsed by the Society for Vascular Medicine. It was the product of a year-long effort to synthesize the best data available regarding CIMT and carotid plaque presence as predictors of CVD risk, with a goal of producing a clinically useful document that provided recommendations for the use of carotid ultrasonography in clinical practice. This document addressed issues of standardization and will help improve the availability of experienced clinical laboratories that can perform highquality CIMT studies in a clinical setting. This paper summarizes the major findings of the ASE consensus statement and updates areas related to the effects of carotid ultrasound on patient and physician outcomes, as well as recent studies evaluating the predictive values of CIMT and coronary calcification.

BACKGROUND Use of carotid ultrasonography to measure CIMT and to detect carotid plaques is a noninvasive, safe, From the School of Medicine and Public Health, University of Wisconsin, Madison, WI;1 and the School of Medicine and the Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD2 Address for correspondence: James H. Stein, MD, School of Medicine and Public Health, University of Wisconsin, 600 Highland Avenue, G7 ⁄ 341 CSC (MC 3248), Madison, WI 53792 E-mail: [email protected]

doi: 10.1111/j.1751-7141.2008.00021.x

well-validated, reproducible technique for quantifying the burden of subclinical vascular disease and assessing CVD risk that increasingly is being used as a clinical tool. Six consensus statements or guidelines have addressed carotid ultrasonography for CVD risk assessment.1–6 Measurement of CIMT is feasible in a clinical setting and can help determine aggressiveness of preventive strategies by reclassifying intermediate-risk patients without coronary heart disease.7–11 Clinicians who plan to use carotid ultrasonography to evaluate CVD risk are encouraged to read the ASE consensus statement in detail and to pay particular attention to the recommendations on patient selection, scanning technique, study interpretation, reporting, training, and certification.1 Highlights of the ASE consensus statement on use of carotid ultrasonography for CVD risk assessment are as follows.

UPDATE ON RISK PREDICTION At the time of the report, 9 published prospective studies with >1000 asymptomatic participants had examined CIMT and CVD risk.12–21 Each study demonstrated that CIMT was significantly associated with risk for myocardial infarction, stroke, death from coronary heart disease, or a combination of these events. In most of these studies, CIMT predicted future CVD events independent of traditional risk factors. An additional report from the Multi-Ethnic Study of Atherosclerosis (MESA)22 confirmed these findings. Furthermore, 9 large studies demonstrated similar or greater predictive power for carotid plaque and CVD.17–21,23–27 In these studies the relative risks and hazard ratios associated with increased CIMT or carotid plaque presence were sufficiently high that their consideration in patients at intermediate CVD risk would be expected to alter risk assessment and use of

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Table. Carotid Ultrasonography for Cardiovascular Disease Risk Assessment: Patient Selection Consider scanning in patients aged 40–70 years, without a condition that indicates high CVD riska, and: • Intermediate CVD risk (ie, 6%–20% 10-year risk of myocardial infarction or coronary heart disease death using the Framingham risk score); • Family history of premature CVD in a first-degree relative; • Individuals older than 60 years with severe abnormalities in a single risk factor who otherwise would not be candidates for pharmacotherapy; or • Women younger than 60 years with 2 CVD risk factors. Imaging should not be performed if the results would not be expected to alter therapy. Abbreviation: CVD, cardiovascular disease. a Such as established CVD or risk equivalent conditions.

risk-reducing interventions. Two recent reports confirmed these findings.28,29 In the ASE consensus statement, CIMT was considered increased if it was in the highest quartile (ie, 75th percentile for a person’s age, sex, and race)1 and nomograms of CIMT values from large, population-based studies in North America and Europe are provided for reference. Carotid plaque was defined as ‘‘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 that is distinct from the adjacent boundary.’’1 This definition is in agreement with studies showing increased CVD risk with plaque presence and previous recommendations.5,23,30,31

PATIENT SELECTION Because measurement of CIMT testing can reclassify patients at intermediate risk, discriminate between patients with and without prevalent CVD, and predict major adverse CVD events,7–11,20,32 carotid ultrasonography can be a useful test for refining CVD risk assessment in the certain types of patients (Table), provided they do not already have conditions that indicate high CVD risk (such as established CVD or risk equivalent conditions). If the level of the aggressiveness of preventive therapy is uncertain and additional information about the burden of subclinical vascular disease or future CVD risk is needed in these patients, it was the consensus that increased CIMT or carotid plaque presence in these patients may justify a change in management, recognizing that it has not been proven that a strategy of imaging to guide preventive strategies is more effective than application of current guidelines without imaging. Imaging should not be performed unless the results would be expected

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to alter therapy. Measurement of CIMT and evaluation for carotid plaque presence is best suited for individuals between the ages of 40 and 70 years; however, there are data for its predictive value in younger and older adults. Repeat studies to evaluate for progression or regression of CIMT are not recommended for use in clinical practice because of technical challenges with repeat scans, measurement variability relative to expected age-related progression rates, and a smaller evidence base for prediction of CVD events in patients without established CVD.

OUTCOMES DATA The data for improvement in CVD outcomes when carotid ultrasonography is used as an imaging strategy are limited to small studies and surrogate end points. When carotid plaques or increased CIMT is discovered, physicians are more likely to prescribe aspirin and lipid-lowering therapy.33,34 Data regarding the effects of subclinical carotid vascular disease on patient intentions, motivation, and adherence to recommendations, however, are mixed.33–35 There is great interest in carotid ultrasonography as a tool to assist with smoking cessation. In a small randomized study, smokers shown photographs of their carotid plaques were more likely to stop smoking after 6 months.36 In an observational study, patients with plaques appeared to be more motivated to quit.37 In another observational study, smokers shown pictures of their plaques engaged in more smoking cessation behaviors; however, only individuals with high levels of self-efficacy had greater intention to quit smoking, emphasizing the complex psychological background that must be considered when attempting to use arterial imaging as a motivational tool.38 Indeed, in the field of atherosclerosis imaging, the critical research question is not whether detection of subclinical vascular disease increases CVD risk—it clearly does. The question that still remains open is whether a strategy that incorporates early detection of arterial disease can improve long-term outcomes. The Measuring Effects on Intima-Media Thickness: An Evaluation of Rosuvastatin (METEOR) study39 does not definitively answer that question, but it does shed some light on the subject. In that randomized clinical trial, middle-aged adults with apparently low to intermediate CVD risk who would not have qualified for lipid-lowering therapy but who were found to have increased CIMT had reduced progression of CIMT with statin therapy. The difference in CIMT progression rates between patients treated with statins and patients receiving a placebo was similar to that observed in secondary prevention trials that were associated with a reduction in cardiovascular events,39,40 suggesting that a strategy of lipid-lowering therapy in individuals with increased CIMT can delay the progression of vascular injury.

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SCANNING PROTOCOL The ASE consensus statement also recommended that when used for CVD risk assessment, carotid ultrasound imaging and measurement should follow the protocol from a large epidemiologic study that reported CIMT values in percentiles by age, sex, and race ⁄ ethnicity. The recommended carotid ultrasound scanning protocol is described in detail. Because the common carotid arteries are straight, superficial, and relatively easy to image in most individuals, CIMT measurements should be limited to the far wall of the common carotid artery; however, the extracranial carotid arteries should be scanned thoroughly for the presence of carotid plaques. Limiting imaging to the common carotid only is not recommended, as it risks missing more significant atherosclerosis in the more distal carotid segments where atherosclerosis progresses more rapidly. Thus, a complete study includes scanning for the presence of plaque followed by assessment of common carotid artery CIMT.

COMPARISON WITH CORONARY CALCIUM SCORING Fast computed tomography is an alternative test that can evaluate subclinical vascular disease by quantifying coronary artery calcium.41 In a recent report from MESA, both increasing coronary artery calcium and CIMT predicted coronary heart disease events; however, the degree of coronary artery calcium was a stronger predictor of coronary heart disease and CIMT was a better predictor of strokes.22 A report from the Cardiovascular Health Study42 found that these tests had similar predictive values for CVD in older patients. Carotid ultrasonography, however, has some potential advantages compared with measurement of coronary artery calcium. Carotid ultrasonography does not involve exposure to ionizing radiation, an important consideration when imaging healthy young and middle-aged adults.43 Also, CIMT is a continuous measure that could be used to stratify risk in women and younger men, as well as in African American individuals, where coronary artery calcium scoring may have limited discriminatory power because of the absence of calcification, which does not imply the absence of CVD risk.44–46 A recent report from MESA showed that the presence of increased CIMT predicted CVD events among individuals without coronary artery calcification.47

INSTRUMENTATION, READING, AND REPORTING Regarding ultrasound instrumentation and technique, a state-of-the-art ultrasound system with a linear-array transducer operating at a fundamental frequency of at least 7 MHz should be used, and B-mode imaging is preferred over M-mode imaging. A small parts ultrasound phantom should be used to ensure accurate calibration of the ultrasound sys-

Figure. Measurement of carotid intima-media thickness of the distal 1 cm of the far wall of the common carotid artery using a semiautomated border detection program.

tem and to determine axial and lateral resolution. Routine preventive maintenance of the ultrasound system should be performed at least biannually. The ASE consensus statement also recommended that imaging should follow a scanning protocol from a large epidemiologic study that reported CIMT values in percentiles by age, sex, and race ⁄ ethnicity (such as the Atherosclerosis Risk in Communities [ARIC] study or others), and that ultrasound images of the distal 1 cm of the far wall of each common carotid artery should be obtained and compared with values from a normative data set (Figure). The CIMT and carotid plaque scanning protocol recommended for most middle-aged adults is provided.1 Other scanning protocols from observational studies with published nomograms may be used; however, the clinical laboratory must have sufficient expertise to perform them accurately and reproducibly. Because of the high likelihood of referral bias and inaccurate risk estimates, use of normative values from clinically referred populations is discouraged. Evaluating for the presence or absence of plaque in conjunction with measuring common carotid artery CIMT offers a better representation of subclinical vascular disease and CVD risk than only measuring CIMT. To measure CIMT, the bloodintima and media-adventitia interfaces of the far wall are traced using a leading edge–to-leading edge method. The reader should be able to see the blood-intima and media-adventitia boundaries clearly with demonstration of a ‘‘double-line’’ sign.48,49 A semiautomated border detection program should be used to measure CIMT and mean values from the far walls of the right and left common carotid arteries should be reported.

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The report should be understandable and the results described in a clinically relevant fashion. It should clearly identify the type of study being performed (ie, ‘‘Carotid Ultrasound Study for Cardiovascular Risk Assessment’’). It should note that it is not a replacement for a clinically indicated carotid Duplex ultrasound and that the results do not indicate the presence or absence of clinically significant obstruction, unless noted otherwise. The ASE consensus statement also recommended that CIMT results be reported as absolute values in mm, accompanied by the broad range of the CIMT percentile, to avoid the appearance of greater precision than is achievable when mapping CIMT values to a reference population.1 The ASE consensus statement described CIMT values 75th percentile as ‘‘high’’ and indicative of ‘‘increased CVD risk.’’1 Values in the 25th to 75th percentile are considered ‘‘average’’ and indicative of ‘‘unchanged CVD risk.’’ Values 25th percentile are considered ‘‘lower CVD risk,’’ but available data do not support a recommendation to modify the intensity of therapy based on a low CIMT value. These levels of risk should be reported. Finally, recommendations for training and certification for readers and scanners are provided.

CONCLUSIONS In conclusion, the ASE consensus statement summarized the evidence base supporting the use of carotid ultrasonography as a CVD risk assessment tool in asymptomatic individuals and broke new ground by providing practical details regarding clinical use of this technique, including recommendations for instrumentation, scanning technique, training of readers and scanners, quality control, study interpretation, and reporting of results.1 Carotid ultrasonography can detect subclinical vascular disease and help identify patients at increased risk for CVD. Strict attention to quality control in image acquisition, measurement, interpretation, and reporting are very important when this technique is used in clinical practice.1 Disclosures: Dr Stein has received research funding from Astra-Zeneca, Siemens Medical Solutions, and Sonosite. He has been a consultant for Siemens Medical Solutions and has intellectual property assigned to the Wisconsin Alumni Research Foundation related to carotid ultrasound and cardiovascular disease risk assessment. Dr Korcarz has served as a consultant for Siemens Medical Solutions. Dr Post has no declarations.

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