Zero CAC Reliably Excludes CAD Among Stable, Symptomatic Patients, but Experts Debate Its Need

For symptomatic patients undergoing CT coronary angiography for suspected stable angina, a zero coronary artery calcium (CAC) score has a high negative predictive value for excluding obstructive coronary artery disease and portends a good prognosis over 2 years, according to a prospective cohort study.

Still, stenoses were confirmed in about 10% of patients with a zero CAC score—including 1.9% with stenoses of at least 50%—prompting the authors, led by Xue Wang, MBBS (University of Cambridge, England), to urge the use of CT coronary angiography in all symptomatic patients without using CAC scoring as a gatekeeper, as suggested in the latest update of the NICE guidelines in the United Kingdom.

“I think calcium scoring has a place in many other areas of cardiology, but for the evaluation of stable patients with chest pain, I think it's best not to do a calcium score and move straight to a CT coronary angiogram as per the guidelines,” senior author James Rudd, MD, PhD (University of Cambridge, England), told TCTMD.

For the evaluation of stable patients with chest pain, I think it's best not to do a calcium score and move straight to a CT coronary angiogram as per the guidelines. James Rudd

Stephan Achenbach, MD (University of Erlangen, Germany), who was not involved in this study, agreed with that assessment. While symptomatic patients have been underrepresented in large trials of CAC scoring, he worries about patients with typical chest pain—but a CAC score of zero—receiving a clean bill of heart health.

With the exception of patients at low-risk for CAD, Achenbach said he agrees with the authors that “if a patient has typical symptoms and the calcium score is zero, I would still do a CT angiogram.”

On the other hand, Leslee Shaw, PhD (Weill Cornell Medical College, New York, NY), who also was not involved with this analysis, said “this study solidifies the role of CAC as a front-line test in symptomatic de novo chest pain patients” who are at low to intermediate risk. “It’s fine to miss 1.9% [given] the money you would spend to identify so few,” she told TCTMD in an email, adding that because obese patients and smokers were more likely to have obstructive CAD in this cohort, “it is reasonable to suggest CTA” in these subgroups.

Study Findings

For the study, published online last week in Open Heart, the researchers prospectively enrolled 1,753 consecutive symptomatic patients who underwent CAC scoring and CT coronary angiography for suspected stable angina at a single institution between 2009 and 2016. Just over half the cohort had zero CAC scores, and these patients were more likely to be younger and female and less likely to have hypertension, diabetes, or a history of smoking.

Of the 751 patients with zero CAC scores who received CT angiography, 89.7% had normal coronary arteries but 8.4% (n = 63) had stenoses less than 50% and 1.9% (n = 14) had stenoses of at least 50%. This resulted in a negative predictive value of 98.1% for a zero CAC score being able to exclude obstructive CAD with a sensitivity of 93.7% and a specificity of 59.7%. Obese patients and those with a history of smoking were more likely to have obstructive CAD with a zero CAC score.

Simply saying that a good calcium score always has a good prognosis is a little cutting the story short because it is very likely that those patients who had a zero calcium score and were included in the trial had a revascularization if they had a stenosis. Stephan Achenbach

For comparison, only 1.3% of those with non-zero CAC scores were deemed to have normal coronary arteries.

After a median follow-up of 2.2 years, the annualized MACE rate was lower for those with zero versus non-zero CAC scores at baseline (1.92 vs 7.37 per 1,000 person-years). The events that occurred within the zero CAC group were either nonfatal MIs or nonelective revascularizations—there were no coronary deaths. While the risks of both MACE (HR 3.8; 95% CI 1.4-10.3) and all-cause mortality (HR 7.6; 95% CI 2.3-26) were higher for patients in the non-zero CAC arm, this finding was no longer statistically significant after adjusted analyses.

Confirmatory Results

Rudd said none of their findings were unexpected.

“Asymptomatic patients generally have a rate of 2-3% of underlying coronary artery disease given a zero calcium score, so to see that go up to about 10% in people with symptoms was not a huge surprise,” he observed. “Having said that, they did have a pretty good outcome in terms of the follow-up that we did. It was a limited, incomplete follow-up and a small number of events I should say compared to some of the vast registries that we've seen recently, but it did show that with a zero calcium score, even if you did have some underlying coronary artery disease, your event rate was very low over the next few years.”

The results “fit nicely” with what was observed in the SCOT-HEART trial given that by identifying the 10% of patients with a zero calcium score and some underlying coronary artery disease means that “we can go on and treat those patients with aspirin or statins or some other preventative measure to try and improve their outcomes,” said Rudd. “By doing just a calcium score, you would miss that opportunity to improve outcomes for those patients.”

Parham Eshtehardi, MD (Emory University, Atlanta, GA), who serves as the social media editor for Open Heart, told TCTMD that the findings should lead the community to question whether a cheap, readily available, low-radiation test can be used to rule out obstructive disease in stable angina patients.

“At this point the discussion is hot, [and] it's a very interesting debate, but I don't think we have enough evidence to make clinical decisions based on the current data,” he said. “Until it goes into the guidelines and becomes something that different societies agree on, we should continue using coronary artery calcium only for primary prevention in low- to intermediate-risk asymptomatic patients.”

For now, Achenbach cautioned against thinking that all patients with a zero CAC score have a good prognosis regardless of obstructive CAD status, because this also depends on treatment.

“The authors say these patients had a good prognosis, nothing happened to them, but what they don't say is whether the stenosis was treated or not,” he said, adding that it is likely that most of them did undergo revascularization. “Then it's no surprise they have a good prognosis. . . . Simply saying that a good calcium score always has a good prognosis is a little cutting the story short because it is very likely that those patients who had a zero calcium score and were included in the trial had a revascularization if they had a stenosis. That part must not be missed.”

Longer Follow-up, More Patients Needed

“This certainly isn't the definitive study in this patient group of people with symptoms, but I'm not sure how many open questions are left,” Rudd said. “Our study was more of a confirmatory study of studies that we mention in the paper like the CONFIRM trial, so I don't necessarily think there's a need for any more just calcium scoring type studies to be done.”

For her part, Shaw said she would like to see “more randomized trials including longer term follow-up of CAC-guided strategies.”

At this point the discussion is hot, [and] it's a very interesting debate, but I don't think we have enough evidence to make clinical decisions based on the current data. Parham Eshtehardi

Eshtehardi agreed, specifically about the need for more work in symptomatic patients. “We need larger studies, we need research in low-to-high risk patients,” he said. “If you . . . include more intermediate- and high-risk patients, then you would have a higher risk and your negative predictive value is then going to go down. So I think we need larger studies that include more intermediate- and high-risk patients.”

Photo Credit: James Rudd. Significant stenosis in the left main coronary artery of a 48-year-old male with stable chest pain symptoms and a zero calcium score.