Published: Nov 22, 2013 | Updated: Nov 24, 2013
By Salynn Boyles, Contributing Writer, MedPage Today

Full Story:  http://www.medpagetoday.com/Cardiology/Atherosclerosis/43082

The density of calcium in coronary artery plaque is inversely and significantly associated with heart disease and stroke risk independent of calcium volume and should be considered whenever calcium scanning is used to assess patient risk, researchers reported.

A new analysis of data from the Multi-Ethnic Study of Atherosclerosis (MESA) trial found that in CT scanning for coronary artery calcium (CAC), Agatston area or volume scores alone were not optimal measures for predicting cardiovascular risk.

“The role of CAC density should be considered when evaluating current CAC scoring systems,” Michael H. Criqui, MD, MPH, of the University of California, San Diego, and colleagues, wrote online ahead of print in the Journal of the American Medical Association .…

“The Agatston score is widely used (in CAC screening) and there is no question that it is predictive,” Criqui told MedPage Today.“But our research shows that considering calcium volume and density scores separately is a better measure of patient risk that may allow us to more appropriately categorize patients as to what kind of treatments they need.”

Despite evidence of the strong predictive value of CAC, there has been little comparison of the different measures of CAC to determine which is most predictive, or whether upweighting a CAC score for greater density adds value, the researchers wrote.

Several studies have suggested that greater calcium density in coronary artery plaque is associated with decreased cardiovascular risk.

A recent study of CT angiography showed that most screened patients with CAC had calcified plaques and that they had a lower risk for coronary heart disease (CHD) than those with unclassified or mixed plaques. And another study examining the impact of statins on plaque stability found a consistent tendency for the statin group to have more CAC progression, indicative of more calcium and less lipid and more stable plaque.

To test the role of CAC density in cardiovascular disease (CVD) risk prediction, the researchers derived a formula to create a CAC density score using individual Agatston scores and volume scores from 3,398 MESA study participants who were between the ages of 45 and 84 and free of known cardiovascular disease at enrollment.

During a median of 7.6 years of follow up, the participants experienced a total of 265 CVD events.

The analysis revealed that with both the CAC volume and CAC density scores in the same multivariate model, the volume score showed an independent association with incident CHD, with a hazard ratio (HR) of 1.81 (95% CI 1.47-2.23) per standard deviation (SD=1.6) increase, an absolute risk increase of 6.1 per 1000 person-years. For CVD the hazard ratio was 1.68 (95% CI 1.42-1.98) per SD increase, with an absolute risk increase 7.9 per 1,000 person-years.

CAC density scores showed an independent inverse association with an HR of 0.73 (95% CI 0.58-0.91) per SD (SD=0.7) increase for CHD, absolute risk decrease of 5.5 per 1000 person-years, and an HR of 0.71 (95% CI 0.60-0.85) per SD increase for CVD, absolute risk decrease 8.2 per 1000 person-years.

Area under the receiver operating characteristic curve analyses showed significantly improved risk prediction with the addition of the density score to a model containing the volume score for both CHD and CVD. In the intermediate CVD risk group, the area under the curve for CVD increased from 0.53 (95% CI 0.48-0.59) to 0.59 (95% CI 0.54-0.64), P =0.02.

There was a stepwise decrease in risk across density score quartiles, with HRs of 0.89 (95% CI 0.53-1.47), 0.79 (95% CI 0.45-1.37), and 0.50 (95% CI 0.27-0.90).

Study limitations cited by the researchers included the use of the arbitrary 4-point scale to assess calcium density rather than the continuous Hu scale and the fact that participants were told their CAC scores at baseline, which could have led to interventions in those with higher scores.

In an editorial published with the study, Philip Greenland, MD, of Northwestern University’s Feinberg School of Medicine in Chicago, wrote that the research shows that “for little additional cost and no additional risk” CVD risk discrimination as measured by CAC scoring can be improved by considering calcium density.

But Greenland added that the improvement is not meaningful enough to justify wider use of CAC testing in asymptomatic people.

Greenland served as chairman for the writing committee that revised the latest American Heart Association/American College of Cardiology guidelines on cardiovascular risk assessment in asymptomatic adults.

Those guidelines state that measurement of CAC is reasonable for cardiovascular risk assessment in intermediate risk adults, defined as those with a 10% to 20% risk of having an event within 10 years.

“Among patients at intermediate risk, those in whom CAC had its greatest utility, 13.9% of patients were correctly reclassified,” he wrote. “Thus, although CAC density scoring can be useful for increasing the discrimination of CAC testing at little or no cost, the evidence on CAC testing in general is not sufficient to justify wider testing based on these relatively modest findings.

• ACCF/AHA 2007 Clinical Expert Consensus Document: Coronary Artery Calcium Scoring By Computed Tomography in Global Cardiovascular Risk Assessment
• Noninvasive Coronary Artery Imaging: Magnetic Resonance Angiography and Multidetector Computed Tomography Angiography

Primary source: Journal of Clinical Endocrinology & Metabolism
Source reference: Yeap BB, et al “In older men an optimal plasma testosterone is associated with reduced all-cause mortality and higher dihydrotestosterone with reduced ischemic heart disease mortality, while estradiol levels do not predict mortality” J Clin Endocrinol Metab2013; DOI: 10.1210/jc.2013-3272.