Coronary Calcium Imaging Improves on Framingham Score Regardless of Symptoms in Analysis

February 10, 2015

HOUSTON, TX — In asymptomatic and symptomatic patients at low risk for coronary artery disease, the use of coronary artery calcium (CAC) imaging improves long-term prediction of risk beyond that established by the Framingham Risk Score (FRS) and exercise-treadmill and stress-perfusion testing, according to the results of a new study[1]. The same findings were observed even among individuals who met the appropriate-use criteria for functional testing, report investigators.

"What we were able to show was that across all Framingham Risk Scores, calcium scoring significantly added in terms of predicting outcome and reclassifying risk in these individuals," senior investigator Dr John Mahmarian (Houston Methodist DeBakey Heart and Vascular Center, TX) told heartwire . "There have been several studies looking at low Framingham Risk Score patients, and this study bolsters the argument that calcium scoring adds tremendously in that [low-risk] group."

Furthermore, the researchers also looked at several treadmill variables—peak-exercise capacity, exercise-tolerance test (ETT) ischemia, and the Duke treadmill score—and found the addition of the calcium score to any of the variables significantly improved the reclassification of risk beyond that achieved with the clinical-data and functional-test results.

The results of the study, which was led by Dr Su Min Chang (Houston Methodist DeBakey Heart and Vascular Center), are published February 9, 2015 in JACC: Cardiovascular Imaging.

Relative Benefits of CAC Scores vs Other Tests

Speaking with heartwire , Mahmarian said the clinical guidelines and appropriate-use criteria both support the use of ETT and single-photon-emission computed tomography (SPECT) for evaluating risk in asymptomatic patients with risk factors for coronary artery disease. CAC screening is considerate an appropriate test in patients with symptoms at intermediate or high risk for coronary disease. At present, there are no studies indicating which of the tests provides the best benefit in coronary-disease detection and long-term risk stratification, say the researchers.

"Over the years, treadmill testing has been used quite frequently in both symptomatic and asymptomatic patients to assess risk," Mahmarian told heartwire . "Calcium scoring over the past 10 to 15 years has grown a large data set demonstrating its tremendous prognostic capabilities based on the presence and extent of calcification in asymptomatic patients. What we wanted to do in this particular study was to look at the relative benefit of a calcium score vs a stress test."

The present study included 988 asymptomatic or symptomatic low-risk patients without prior coronary artery disease, all of whom underwent CAC screening, ETT, and SPECT testing. The average age of patients was 57 years, and nearly all had at least one risk factor for coronary disease. Overall, there was a mix of patients based on the 10-year FRS, with 160 patients considered low risk, 655 classified intermediate risk, and 131 at high risk. At baseline, 88% had no ETT ischemia and 89% had a normal SPECT. The mean CAC score was 118 and the median follow-up was 6.9 years.

The cardiac-event rate, a composite of cardiac death, nonfatal MI, and the need for coronary revascularization, was 11.2%. Individuals who had an event had a higher mean FRS and CAC score, were more likely to have ETT ischemia or an abnormal SPECT, and also had a lower Duke treadmill score than those who did not. In a multivariate-adjusted model, abnormal SPECT, ETT ischemia, decreasing exercise capacity, a low Duke treadmill score, and increased coronary calcification were significant predictors of cardiac events in the entire cohort and in the 824 patients who met the criteria for functional testing.

Overall, the addition of the CAC score to the FRS reclassified risk in 50.7% of individuals. The addition of the CAC score reclassified risk in 69.2%, 65.8%, and 72.9% of patients when added to the risk models using ETT, SPECT, and Duke treadmill score, respectively. The addition of CAC scoring significantly increased the overall net reclassification index (NRI) when added to the FRS, as well as risk-classification models with SPECT or ETT variables. The integrated discrimination improvement (IDI), which measures the incremental prognostic value of the CAC score to an existing model, was also significantly improved when CAC was added to the ETT, SPECT, and Duke treadmill score.

The researchers noted that 80% of patients were classified as low risk based on the treadmill-test results in terms of no ischemia, a low Duke score, or high peak-exercise capacity as measured by metabolic equivalents (METS). Even in this low-risk group, calcium scoring segregated and was able to define who was high risk and who was low risk. For example, in patients without ETT ischemia, the adjusted event rate increased from 0.56% among those with a CAC score <10 to 3.15% among those with CAC score >400. Among individuals with a low Duke treadmill score, the event rate increased from 0.58% per year among individuals with a calcium score <10 to 3.0% among individuals with a low Duke treadmill score but a CAC score >400.

"What it basically shows is that irrespective of the exercise-treadmill test and SPECT results, the calcium score was the one that really defined risk," said Mahmarian.

Based on the findings, the researchers say that CAC screening should be the "first-line test" over exercise-treadmill testing or SPECT for the assessment of risk in this low-risk cohort.

"Our algorithm for an asymptomatic patient who has risk factors for coronary disease would be a calcium test first to define their risk," Mahmarian told heartwire . "If they have calcification, they need to be aggressively treated. If they have a very high calcium score, then they should probably go on to have further testing, such as myocardial perfusion imaging, to make sure they don't have ischemia."

Progress Toward Personalized Medicine

In an editorial[2], however, Dr Leslee Shaw (Emory University, Atlanta, GA) notes there are limitations to making CAC imaging a front-line test.

"These concepts of identifying risk, altering risk with ischemia-guided management, and reducing the prognostic significance of the exercise ECG are the intended goals of testing for and treating stable ischemic heart disease within the diagnostic workup," writes Shaw. "In many ways, the fact that we can intervene in ischemia renders it integral for guided management."

She notes there is no similar-guided management approach following CACS, and this is the reason it is so prognostically significant in this long-term analysis. "The lack of an established therapeutic strategy following CACS limits our enthusiasm for making CACS a front-line test," writes Shaw.

She suggests a potential management approach that utilizes the atherosclerotic burden as measured by CAC with exercise-test findings to devise an ischemia-guided management strategy. The "interplay" between markers of ischemia and atherosclerosis could form a diagnostic strategy that is seen in patients tested and evaluated over a period of years.

"[The] results, given their longevity in risk prediction, could form the basis of intensive and serial risk evaluations for years following an index diagnostic evaluation," said Shaw. "As we progress toward personalized medicine, including patient-centered imaging, guided diagnostic risk evidence should form the basis of ensuing short- and long-term management. We and others have advocated that the link between imaging and improving outcomes is largely indirect and that outcomes can be improved only if imaging-guided therapeutic intervention is implemented."

Chang, Mahmarian, and coauthors report they have no relevant financial relationships, as does Shaw.

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