Roslyn, NY - A long-time advocate for coronary artery calcium scoring says a new, large, long-term, prospective study linking calcium scores, CRP, and coronary events should put an end to the debate over whether calcium identified by electron beam computed tomography (EBCT) adds anything to modern-day risk-factor profiling [1].

"For about five years now, close observers of the field would agree that the calcium score predicts coronary artery disease [CAD] events," senior author on the study, Dr Alan D Guerci (St Francis Hospital, Roslyn, New York), told heartwire. "What was disputed was whether the calcium score predicted coronary disease events independently of standard risk factors. Our study demonstrates that yes, indeed, the calcium score does predict CAD events independently of standard risk factors and in addition predicts those events more accurately than standard risk factors."

But Dr Scott Grundy (UT Southwestern, Dallas, TX), who wrote an editorial accompanying the study [2], told heartwire that Guerci et al's paper "is not the last word" even if "everybody likes to think their own study is the last word."

Still, says Grundy, "I think they did a huge study and should be congratulated on a very good study. They've demonstrated that there is a potential use for calcium scoring in people who are at intermediate risk, who are in this zone of moderately high risk between 10% and 20% by Framingham score [reflecting risk of having a coronary heart disease event over a 10-year period]. . . . I have to say that they did the right study, but it's not the only study that ultimately should be done to address this question."

The St Francis Heart Study, a natural-history study, with lead author Dr Yadon Arad (St Francis Hospital), appears in the July 5, 2005 issue of the Journal of the American College of Cardiology.

Arad et al's study is the first community-based, large-scale, prospective study to enroll almost 5000 unselected participants, age 50 to 70 years of age, with no known coronary disease. The follow-up, completed in 4613 patients, encompassed a mean of 4.3 years: during this period, 119 participants had a coronary event. Analysis showed that coronary calcium scores were higher in people who had coronary events than in those who didn't. Using a cut-point calcium score of 100, participants with scores over 100 were almost 10 times more likely to have an "atherosclerosis cardiovascular disease event" (an end point that included stroke and peripheral vascular surgery) and even more likely to have a CAD event.

Of note, the coronary calcium score predicted CAD events independently of CRP and standard risk factors and was superior to the Framingham risk index for predicting events. By comparison, after adjustment for standard risk factors alone or in combination with baseline calcium score, CRP did not predict CAD events. In recent years, critics of calcium scanning have charged that the imaging results might be as good as or better than "traditional" risk factors such as age, sex, and history of smoking but were no match for risk predictors, CRP among them.

Quite frankly, for middle-age whites, the debate is over.

Guerci acknowledged that CRP has a mammoth body of evidence behind it—much more so than EBCT for calcium scoring—yet all indicators point to calcium scoring as being a stronger predictor of risk. "There's no doubt that CRP is an independent risk factor, but there's also no doubt that it's a relatively weak independent risk factor," he commented. What's more, "this study demonstrates that coronary artery calcium predicts coronary disease events independently of, and more accurately than, standard risk factors, but not so powerfully as to negate the value of the standard risk factors."

Tallying up the evidence, Guerci pointed out that there are now approximately 11 studies supporting a role for calcium scoring in risk prediction, at least in people at intermediate risk of coronary events. "Quite frankly, for middle-age whites, the debate is over," he stated.

In an interview with heartwire, Grundy acknowledged that calcium scoring has had a tough row to hoe in proving itself as a risk prediction tool, based largely on the controversy surrounding the aggressive marketing of calcium scans during the 1990s, before their predictive accuracy was established.

"There has been a high level of skepticism surrounding the field of coronary calcium, with a lot of people put off by this aggressive marketing and overinterpreting of the data," Grundy commented. "People find out they have a little bit of coronary calcium, and they get panicked and go to their cardiologists to get an angiogram, and inappropriate things have happened. For that reason, a lot of cardiologists think it's not of much utility. I would say that in the past few years, there has been a greater acceptance of coronary calcium as a marker for risk, when used appropriately."

Guerci, too, agrees that the marketing of EBCT scans harmed more than it helped. "There's no doubt that some of the scanning centers around the country have engaged in ethically questionable advertising practices, but the marketing of this test and the science behind it are easily separated, and it has disturbed me all along that some of the critics of this test have not made that distinction as clearly as I think it could, and should, be made."

I personally believe a calcium scan is a good idea, and if it were readily available to me, which it's not, I would use it sometimes.

The best solution, says Grundy, is for the test to be used appropriately. "If your patient has a full risk assessment and is found to be at intermediate risk and, because you're not sure where the patient stands, you refer the patient for a coronary artery calcium test, understanding that a calcium score is a risk factor that adds to the regular risk factors, not a indication that the patient needs an angiogram or anything like that, then I think you're using it in a rational way."

Grundy adds: "I personally believe a calcium scan is a good idea, and if it were readily available to me, which it's not, I would use it sometimes. On the other hand, it should be done as a referral; it shouldn't be done through advertising."

Grundy's editorial points out that the St Francis studies, beyond supporting a role for coronary artery calcium scoring in people at intermediate risk, also suggest a need for revised atherosclerotic cardiovascular disease end points in clinical trials. This was particularly obvious for the St Francis randomized trial, in which total coronary heart disease events (CHD) and "hard" CHD events were only 2.03% and 0.77% respectively, in the placebo group—"only about half of those projected from Framingham risk scoring," he notes.

"There appear to be fewer nonfatal MIs and coronary deaths than in the past, at least according to projections from Framingham scoring," Grundy writes. It may be that people with early atherosclerotic disease are receiving earlier and more intensive interventions, he notes, at the same time that fewer people are dying.

As he told heartwire, "There's a changing picture of presentation of CHD, and I think what this study illustrated is that you're going to have to either broaden the end point of trials to include a lot of other things if it's going to be the same size, or you're going to need much bigger, longer trials. And that's an enormous problem, because they are so expensive to carry out."