Background—
Coronary artery calcium (CAC) measured by computed tomography (CT) has strong predictive value for incident cardiovascular disease (CVD) events. The standard CAC score is the Agatston, which is the product of the within slice CAC plaque area and a plaque specific density factor of 1, 2, 3, or 4, summed for all CT slices. Thus, the Agatston score is weighted upward for greater CAC density. However, data from both observational studies and randomized trials suggest increased CAC density
per se
may be protective for CVD.
Methods—
In a multi-ethnic population of 3398 men and women with Agatston scores > 0 at baseline, we derived a formula using the individual Agatston scores and the volume scores to create a per participant CAC density score. We then analyzed the independent associations of CAC volume and CAC density with incident hard CVD, defined as MI, resuscitated cardiac arrest, cardiac death, stroke, or stroke death,
Results—
During a median of 7.6 years of follow-up, there were 265 hard CVD events, 175 of which were coronary heart disease (CHD) events. In a proportional hazards model including the General Framingham Risk Score (GFRS) and both the CAC volume and CAC density score, the CAC volume score showed a strong independent association with incident CVD, with a hazard ratio per natural log standard deviation increase of 1.62, p<.0001. Conversely, the CAC density score showed an independent association that was strongly protective for CVD, with a hazard ratio per standard deviation increase of 0.72, p<.0003. Multivariate quartile analyses showed that at any given volume score, a density score in the 4
th
quartile (range 3.2 to 4.0) decreased the risk of a CVD event by 51%, p=.002. The density score showed no significant interactions with either sex or ethnicity. The addition of the volume score to the model containing the GFRS increased the area under the ROC curve (AUC) from 0.664 to 0.6869, p=.015, and further addition of the density score increased the AUC to .6994, p=.023. Separate analyses limited to CHD events showed similar results.
Conclusions—
At any given volume of CAC, increased density in calcified coronary plaques is protective for incident CVD, consistent with the concept that calcium deposition may increase the stability of atherosclerotic plaques. CAC scoring systems should be modified to weight downward for density rather than upward, and thus improve CVD risk prediction.
Calcium density score
