Q&A: Calcium score has place, but CTA soft plaque imaging identifies silent risk

Jason L. Kelly, MD, and colleagues at Radiology Imaging Associates in Englewood, Colo., have found that slightly more than half of the patients in their study with a calcium score of zero also had some soft, or vulnerable, plaque seen by coronary CT angiography. Ten percent of those had moderate or severe stenosis.

Of the 729 patients they retrospectively reviewed, they found that coronary CTA identified soft plaque on all 404 studies with abnormal calcium scores. They concluded that the false-negative rate of 29 percent for any plaque in the patient population underscores the limitations of calcium scoring. The study appears in the July issue of the American Journal of Roentgenology.

In an exclusive interview with Cardiovascular Business, Kelly discussed the study, why the time has come for coronary CTA screening and its relevance to the death of “Meet the Press” host Tim Russert.

Cardiovascular Business: Have your findings changed the way you image patients with chest pain or those suspected of having coronary artery disease?

Kelly: The study findings really highlight the value of looking directly at the coronary arteries themselves rather than relying on secondary markers of atherosclerosis. With the advent of coronary CTA, we now have an outstanding non-invasive tool that can see plaque we could never see before. People with acute chest pain characteristic of a myocardial infarct should not be getting a CTA. Those patients should go straight to the cath lab and have the definitive treatment. However, there are a lot of cases where the cardiologist doesn't think a patient is having an MI and doesn't want to subject him or her to an invasive angiogram, but would like to make sure they're not missing something. These patients with atypical chest pain are great candidates for coronary CTA. 
I also feel that coronary CTA is a great test for patients with suspected CAD. Almost every other available test relies on indirect means of assessing disease. Risk factors – things like age, gender, cholesterol, diabetes and blood pressure – generate a probability that disease is present. But they can’t tell a specific patient whether or not they have disease. 
Calcium scoring got us a step closer to looking at actual plaque, but it’s the wrong plaque. The plaque which ruptures and causes acute coronary syndromes is the soft, inflammatory plaque. Calcium score CT uses normograms to assess the probability of disease from the amount of calcium in the coronaries. Again, this is estimating how much dangerous plaque is present by using a secondary marker, calcification.
Cardiovascular Business: Where does invasive angiography fit into the picture?

Kelly: Invasive angiography has been used to validate the findings of calcium score CT, but we now know that angiography is not really the gold standard for plaque assessment.  Angiography can’t see the plaque itself; it can only see narrowing of the lumen. From this, we infer that plaque is the culprit. However, luminal narrowing is a relatively late finding in atherosclerosis. Plaque forms in the blood vessel wall and vessels expand to accommodate it. In our paper, we show an example of a large soft plaque which was obvious on coronary CTA but was not seen on invasive angiography (see images). While the real gold standard for plaque detection and characterization has become intravascular ultrasound, this technique is quite cumbersome and invasive.
For patients and physicians, the key is that coronary CTA is a very sensitive and accurate plaque detector that adds diagnostic certainty previously unavailable. Early identification of potentially dangerous plaque should be the corner-stone of atherosclerosis management. A simple analogy might be crossing the street: you could figure out statistics about how often people get run over crossing a street (i.e., use risk factors), or you could just look and see if there’s a car coming (i.e., use coronary CTA).

A 56-year-old woman presented for coronary CT angiography because of a strong family history of heart disease. Coronary CTA image shows a large soft plaque in mid left anterior descending artery (arrow). Corresponding catheter angiogram (arrow points to region of plaque seen on coronary CTA) did not identify this plaque. In retrospect, there may be mild narrowing in region of plaque on angiography. Source: Image and caption by permission of the American Roentgen Ray Society.  

Cardiovascular Business: Can you call to mind any studies which examined the cost-effectiveness of performing coronary CTA instead of or in addition to a calcium score?  

Kelly: I'm not aware of any studies comparing the cost-effectiveness of coronary CTA versus calcium scoring. In our study, we were surprised to find soft plaque in half of our patients with a normal calcium score, and a significant stenosis in 3 percent of them.  That means that one out of every 25 “normal” calcium score CTs is missing a significant lesion. I'm not an economist, so I can't really tell you if it's cost effective or not to find that undetected plaque and stenosis, but if it were me or my family, I'd want to know.  That being said, calcium scoring has proven prognostic value, it’s just that now there is a better test.

One major concern with coronary CTA is the relatively high cost of the exam, which is between $1,000 and $1,200 for patients paying out-of-pocket. However, the cost of statin therapy alone is at least $1,000 per year, so patients considering therapy who have a negative coronary CTA could recoup the cost of the examination within one year. Cost savings could be considerable when applied to the number of patients eligible for lipid-lowering therapy. The savings are only amplified when the treatment regimen for atherosclerosis may involve multiple drugs – statins, niacin, aspirin, anti-hypertensives, cholesterol absorption blockers, fibrates and Omega-3 fatty acids—which are not without side-effects and could incur significant expense.  

On the other end of the spectrum, invasive angiograms cost three to five times what a coronary CTA does. Additionally, more than one-third of patients undergoing diagnostic angiography have normal or near-normal results. Furthermore, because coronary CTA is able to see plaque growing in the artery wall much earlier than can be seen on invasive angiography, it is able to give a truer picture of the arteries.

Cardiovascular Business: How much of a concern is radiation exposure from coronary CTA?
Kelly: Radiation is big concern. In our practice, using single-source 64-detector scanners, dose modulation and retrospective gating, the median patient dose was 12 mSv in more than 1,200 scans – significantly less than a nuclear medicine stress test. With the advent of prospectively-gated scanning and dual-source scanners, coronary CTA radiation dose has the potential to drop dramatically in the near future.
Once it drops, coronary CTA will be an ideal screening test. Although the supporting data is not yet available, I would guess that people could be screened every 10 years since we know that atherosclerosis develops over decades, starting as fatty streaks in teenagers.   

Cardiovascular Business: In light of the death of political journalist Tim Russert, would you recommend coronary CTA scanning for certain high-risk populations?

Kelly: Russert’s physicians were “surprised” by the amount of plaque in his coronaries given his normal stress test and benign clinical picture. Coronary CTA would have diagnosed his severe disease and he may have gone on to life-saving therapeutic intervention. My understanding is that he had a positive calcium score CT, so he wasn’t a case of being mislead by the absence of coronary calcification. He was a tragic example of how coronary artery disease plays out all too often. It’s a disease that is often clinically silent until it is fatal. I think of heart disease as a disease of halves: half of us will die of it; half of us won’t know we have it until our first heart attack; and half will die from our first heart attack. 
For more coverage of the study, please click here.