The amount of coronary artery calcium (CAC) on a computed tomography (CT) scan provides strong and incremental information as to cardiovascular disease (CVD) risk status beyond standard CVD risk factors. The Agatston method is the standard CAC scoring methodology. For a given CAC volume, the Agatston score is increased 2, 3, or 4 fold based on reaching selectively higher CAC density cutpoints, thus """"""""upweighting"""""""" the Agatston score for greater CAC density. However, extensive evidence exists that densely calcified coronary plaques may pose a lower CVD risk than less densely calcified plaques. As examples, 1) persons who have only calcified plaques have a relatively low risk of CVD 2) patients with unstable angina have fewer calcified plaques than patients with stable angina, and 3) statin treatment may increase Agatston score compared to a placebo group. In preliminary studies, our group has explored CVD risk in two large cohorts, the Multi-ethnic Study of Atherosclerosis (MESA) and the LifeScore Study. Preliminary analyses in both MESA and LifeScore have shown that the volume score, which ignores density, was slightly more predictive than the Agatston score for CVD events. We then created a density score and have shown that CAC density is actually protective for future CVD events at any given CAC volume. In addition, in a case-control study of CVD death in LifeScore, we have shown that a simplified un-weighted score measured on standard chest CTs, the ordinal score, was a better predictor than the Agatston score, particularly at the higher end of the score range. In order to determine the optimal scoring system or systems for CAC from CT scans, we propose to compare four CAC scoring systems in both the MESA and the LifeScore Study. The first two scores will be the volume and ordinal scores discussed above. The other two scores will be newly developed in MESA and validated in LifeScore and both will employ """"""""reverse density weighting"""""""". Rather than """"""""upweighting"""""""" the score for more dense calcified plaque as the Agatston score does, these two scores, called the volume-2 and the ordinal-2 scores, will empirically """"""""downweight"""""""" the CAC score for denser plaques;that is, less dense plaques will produce a higher score and denser plaques a lower score, the opposite of the Agatston method. The volume-2 and ordinal-2 scores will also consider the number of coronary arteries and the specific coronary arteries with CAC. They will be empirically developed in MESA and validated in LifeScore. We will then compare CVD prediction by these four scores in terms of the strength and statistical significance of the hazard ratios, the areas under Receiver Operating Characteristic curves, and the Net Reclassification Index. Finally, in the LifeScore study we will then compare the results when the scores are calculated on electrocardiographic gated cardiac CT scans vs. standard chest CT scans. If CAC measured on standard chest CTs is equally predictive of CVD events as CAC measured on cardiac CTs, CAC assessment could become more widely available, technically easier, and done with a lower radiation dose.

Public Health Relevance

Measurement of coronary artery calcium by computed tomography has proven to be an important predictor of future cardiovascular disease, and in particular coronary heart disease which can lead to heart attacks. This research will compare various methods of measuring coronary calcium and test which methodology is the best in predicting cardiovascular disease in two large cohort studies. This research will lead to more accurate estimate of an individual's risk of cardiovascular disease, and will lead to changes in the clinical care of patients.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Cardiovascular and Sleep Epidemiology (CASE)
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Reis, Jared P
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University of California San Diego
Family Medicine
Schools of Medicine
La Jolla
United States
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Hughes-Austin, Jan M; Dominguez 3rd, Arturo; Allison, Matthew A et al. (2016) Relationship of Coronary Calcium on Standard Chest CT Scans With Mortality. JACC Cardiovasc Imaging 9:152-9
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Blair, Katherine J; Allison, Matthew A; Morgan, Cindy et al. (2014) Comparison of ordinal versus Agatston coronary calcification scoring for cardiovascular disease mortality in community-living individuals. Int J Cardiovasc Imaging 30:813-8
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