Clinical Benefits of Screening Imaging for Asymptomatic Atherosclerosis

By Merle Myerson, MD, FACC

Dr Myserson is Director of Preventive Cardiology, St. Luke's-Roosevelt Hospital, Columbia University College of Physicians and Surgeons, NY.

We currently screen for cardiovascular (CV) disease using algorithms for major risk factors. Most widely used is the decades-old yet successful Framingham risk score, based on total cholesterol, high-density lipoprotein cholesterol, age, gender, smoking status, and systolic blood pressure. The problem with algorithms based on major risk factors is their limited precision. The Framingham score cannot accurately predict events beyond 10 years or in younger populations at low absolute risk but high relative risk.

Atherosclerosis imaging offers an option that is independent of algorithms. Imaging also holds great promise for risk assessment—identifying patients in whom drug intervention for primary prevention is appropriate.

Testing asymptomatic people raises several questions: Does the test provide additive prognostic information to that obtained from traditional risk factors? Is the use of the test associated with improved outcomes? Is the test cost-effective? Other points include unnecessary use in lower-risk persons, and what has been called the "slippery slope to invasive testing," where findings on one test lead to more testing.

Among the imaging modalities currently used to detect subclinical atherosclerosis, 3 techniques are of particular interest in the clinical setting:

• Computed tomography (CT) to assess coronary artery calcium (CAC)
• Ultrasound measurement of carotid intima-media thickness (CIMT)
• Ultrasound to measure brachial artery flow-mediated dilation (FMD).

CT for Coronary Calcium

Measuring CAC has clinical benefit, in part by formulating a "calcium score" that guides us on what to do with the results. CAC is part of the development of atherosclerosis; it occurs almost exclusively in atherosclerotic arteries and is absent in the normal arterial wall. There is a positive correlation between the amount of calcium and the percent of luminal narrowing at the same anatomic site, but the relationship is nonlinear and has large confidence limits.

Imaging techniques: Electron-beam CT and multidetector CT are the primary fast CT methods for measuring CAC. Both techniques involve thin-slice CT imaging using fast scan speeds to reduce motion artifacts. The entire procedure takes 10 to 15 minutes. The radiation is about equal to that of a thoracic CT scan but only 10% of that used in diagnostic coronary angiography. No contrast is needed.

The cost to the patient is approximately $400 and is not covered by Medicare or most other types of insurance. No time frame has been established for repeat testing.

The following calcium scoring system provides the evidence for atherosclerotic plaque: 0 = evidence of no plaque; 1-10 = minimal evidence; 11-100 = mild evidence; 101-400 = moderate evidence; >400 = extensive evidence of plaque.

The evidence: A number of studies have shown the predictive value of calcium scores in asymptomatic people. In the St. Francis Heart Study,¹ calcium scores were independently predictive of outcome above and beyond historical/ measured risk factors. Taylor et al² found that CAC was associated with an 11.8-fold increased risk for incident coronary artery disease (CAD), after controlling for Framingham risk factors. The risk for coronary events increased incrementally across tertiles of CAC severity and added independent prognostic value in predicting events.

There are no established guidelines regarding what to do with each calcium score. A recent study is helpful.³ In this study, 1153 patients had CT evaluation for CAC and exercise myocardial perfusion scintigraphy within the same 6-month period. Based on the results, the authors concluded that in patients with a nonischemic nuclear study, high CAC scores do not confer an increased risk for cardiac events, and a normal nuclear study suggests no need for more aggressive interventions.

Conclusion: Based on the existing evidence, the American College of Cardiology/American Heart Association issued a new consensus statement, saying⁴:

• Asymptomatic persons with an intermediate Framingham risk score may be reasonable candidates for CT assessment of CAC as a potential means of modifying risk prediction and altering therapy
• Little can be gained by testing patients with low Framingham risk scores
• Patients known to be at high risk should always be treated aggressively and would not need a CAC score
• High-risk individuals should not be excluded from aggressive treatment based on a low CAC score.

Ultrasound for CIMT

The benefits of using ultrasound to measure CIMT thickness have been known for some time. This method has been used clinically in the setting of symptomatic cerebrovascular disease or asymptomatic carotid bruit to identify significant obstructive disease. Large observational and epidemiologic studies have shown that CIMT measures correlate with CV risk, and CIMT is an independent marker for CV event risk.

Imaging technique: CIMT is measured by high-resolution B-mode ultrasonographic imaging. It is very user-friendly and involves no radiation or contrast, is quick and completely noninvasive, and is relatively inexpensive. Testing costs approximately $200 and may be reimbursed by insurance.

There is no scoring system, but the definition of abnormal is related to age-adjusted, gender-specific values. Significant changes in CIMT can be seen in 6 months, depending on patient population and treatment, with most changes seen at 1- to 2-year intervals.

The evidence: In the Rotterdam Study involving 7983 adults,⁵ stroke risk increased gradually with increasing CIMT. In the Atherosclerosis Risk in Communities (ARIC) study,⁶ CIMT was consistently greater in participants with prevalent clinical CV disease in a group of 13,870 black and white men and women free of known disease at baseline. A meta-analysis looking at 8 studies concluded that CIMT is a strong predictor for future vascular events. The relative risk per CIMT difference is slightly higher for stroke than for myocardial infarction (MI).⁷

In addition to predicting stroke and MI, CIMT can differentiate between soft, calcific plaque, and fibrocalcific plaque. Ultrasound findings of carotid plaque have been shown to be very close to histological findings and to be better than angiographic imaging.⁸ In 144 patients undergoing angiography who also had CIMT, the positive predictive values for CAD were 45%, 48%, and 75% in patients with increased CIMT, fibrous plaque, and calcific plaque, respectively. The presence of calcific plaque was a better predictor for CAD than that of fibrous plaque and increased CIMT.⁹

Conclusion: Measurement of CIMT is very cost-effective and has minimal risk to patients. It has extensive support in the literature and is useful as a predictor of risk for MI and for stroke. The use of CIMT for research is well established, but the clinical use is still evolving.

Ultrasound for Brachial Artery FMD

Many studies have underscored the importance of endothelial function in vascular biology in both healthy and disease states. An important function of endothelium is to release factors that control vascular tone. Compromised vasodilation due to endothelial dysfunction is associated with atherosclerosis and hypertension.

Imaging technique: Brachial artery FMD ultrasound imaging is low cost, and radiation and contrast free. Baseline images are obtained. The brachial artery is occluded for 5 minutes using a standard adult pressure cuff. Postocclusion ultrasound images are then taken, and the images are analyzed by a computer program. Depending on patient population and treatment, significant changes can be seen after 1 week, but the optimal time frame appears to be 6 weeks to 3 months.

There are no established cut points for FMD. Yeboah et al comment that "brachial artery FMD is variable, owing to physiological factors and technical problems encountered during measurement."¹⁰ Higher values correspond to better endothelial function.¹¹

The evidence: In the Huang study,¹¹ patients with CV events had lower FMD than those without. Participants in the Cardiovascular Health Study underwent FMD and were followed for 5 years. Vascular events were higher in those with FMD greater than or equal to sex-specific medians. FMD has been used as a surrogate marker for reduced risk after treatment. Thirty-three patients with hyperlipidemia were randomized for 6 weeks to atorvastatin (Lipitor) or to placebo. In patients who already had an impaired baseline FMD, atorvastatin treatment resulted in improved FMD.¹²

Conclusion: FMD is a relatively new method for assessing subclinical atherosclerosis. It does not involve radiation and is quick and easy to perform. The clinical utility has not been established.

Summary

The clinical benefit of measuring CAC, CIMT, and brachial artery FMD is evolving, as is the field of screening for subclinical atherosclerosis in asymptomatic persons. Position statements have concluded that these tests should be:

• Used for persons at "intermediate risk" for CV disease
• Performed by those who meet published standards for training and experience
• Performed in high-quality labs.

Atherosclerotic imaging holds great promise for risk assessment, especially to identify patients in whom intervention would be appropriate.

References

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