JACC Feature: Multiple CAC scans predict mortality

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Serial coronary artery calcium (CAC) scans showing calcium progression have prognostic significance for all-cause mortality. However, how to use this information and what therapies may be of value remain unknown, according to a study in the December issue of the Journal of the American College of Cardiology: Imaging.

"This is the first large study following patients for one to 16 years and submitted to repeat CT scans demonstrating incremental increase in mortality with progression of CAC over baseline score, time between scans, demographics and cardiovascular risk factors," the authors wrote, adding that it confirms previous smaller studies.

Matthew J. Budoff, MD, director of cardiac CT at UCLA Harborview Medical Center in Los Angeles, and colleagues assessed 4,609 consecutive asymptomatic individuals with electron beam tomography (EBT) who were referred by primary care physicians for CAC measurement. Patients underwent sequential scans at least 10 months apart and the repeat scans were ordered by their primary physicians to assess change in atherosclerosis risk over time.

Researchers also looked at three ways that progression of CAC is assessed:

  • The absolute difference between follow-up and baseline CAC score;
  • Percent annualized differences between follow-up and baseline CAC score; and
  • Difference between square root of baseline and square root of follow-up CAC score greater than 2.5 (the "SQRT method").

They found that progression of CAC in those with a baseline CAC score greater than zero was significantly associated with mortality regardless of the method used to assess progression.

After researchers adjusted for baseline score, age, sex and time between scans, the best CAC progression model to predict mortality was the SQRT method, followed by a greater than 15 percent yearly increase.

"We had a big enough cohort to determine that all three methods of assessing calcium progression work. Any way you look at it, CAC progression is associated with death," Budoff said in an interview.

A baseline CAC score of zero was not predictive of progression or all-cause mortality. "This further validates the concept that a baseline zero score has a significant warranty period for both future cardiovascular events and progression of atherosclerosis," Budoff said.

In a previous study noted by Budoff, Min et al suggested that a CAC score of zero "affords at least a five-year warranty period, and our study strongly supports that evidence with even longer follow-up and interscan periods."

What unique characteristics do those with zero CAC scores have? "We don't know," Budoff said. "We will have to use carefully designed studies such as MESA [Multi-ethnic Study of Atherosclerosis] to determine differences between people who stayed at zero long term and those that converted. One analysis of MESA data suggested a relationship with incident calcium and traditional risk factors, but nothing about characteristics of individuals who don't calcify over time. Are they genetically different or do they have a certain lipid profile or is there something else that identifies them as being unique? We don't know that yet, but such information would be very helpful to the field."

In the current study, nearly three-quarters of the participants were men, and the overall average age was 60.

"You can extrapolate our results to pertain equally to women as men, even though there were only 25 percent women in our study," Budoff said. "It's a large study, so we still had more than 1,000 women. In addition, other studies have shown that calcium in men and women is predictive of negative results."

In future studies, researchers should keep in mind that women generally present with calcium about 11 years later in life than men, Budoff said. "This is a factor that needs attention when designing such studies."

In the current study, more women and younger men tended to have baseline CAC scores of zero, he said.

The prevalence of cardiovascular risk factors in the current study was high: current tobacco use (6.2 percent), diabetes (7.1 percent), high blood pressure (23.6 percent), hypercholesterolemia (41.2 percent) and family history of coronary artery disease (40.4 percent).

Despite having other risk factors, however, the CAC score was a strong independent predictor of mortality and mortality significantly increased with increasing CAC score.

Out of the 4,609 individuals scanned, there were 288 deaths. Broken down, there were 236