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Coronary Artery Calcium Density and Risk of CV Events
Quick Takes
- Very dense calcified coronary plaque on chest CT is associated with reduced CV events, and CV risk factors including diabetes are inversely associated with plaque density, while statins and physical activity are positively associated with plaque density.
- It is not reported but relatively simple to provide the density score. CAC density score = Agatston score ÷ area score.
- The clinical application of CAC density has yet to be defined. In the future, integrating common clinical risk predictors from the new AHA PREVENT and adding biomarkers hsCRP and Lp(a) and CAC density may provide a much more accurate CVD (coronary and stroke) risk assessment.
Study Questions:
Is coronary artery calcium (CAC) density by computed tomography (CT) inversely associated with plaque vulnerability and atherosclerotic cardiovascular disease (ASCVD) events (coronary heart disease [CHD] and stroke)?
Methods:
The Agatston scoring method for CAC measures each discrete plaque area in mm2. Each discrete plaque area is then multiplied by 1, 2, 3, or 4, depending on the highest density measurement in Hounsfield units (HU) anywhere in the plaque. Plaques with a maximum density of 130-199 HU are multiplied by 1, those with 200-299 HU by 2, those with 300-399 by 3, and those with ≥400 HU by 4. CAC density score = Agatston score ÷ area score.
Electronic databases were searched for studies reporting CAC density and subsequent CVD or CHD events. Random-effects models were used to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses were performed with studies stratified by CVD versus CHD events and by statin use.
Results:
Five studies with six cohorts met inclusion criteria. In total, 1,309 (6.1%) CV events occurred in 21,346 participants with median follow-up ranging from 5.2-16.7 years. Higher CAC density was inversely associated with risk of CV events following adjustment for clinical risk factors and CAC volume (HR, 0.80 per standard deviation [SD] of density [95% CI, 0.72-0.89]; p < 0.01; I2 = 0%). There was no significant difference in the pooled HRs for CVD versus CHD events. The protective association between CAC density and event risk persisted among statin-naive patients (HR, 0.79 per SD [95% CI, 0.70-0.89]; p < 0.01) but not statin-treated patients.
Conclusions:
Higher CAC density is associated with a lower risk of CV events when adjusted for risk factors and CAC volume. Future work may expand the contribution of CAC density in CAC scoring, and enhance its role in CVD risk assessment, treatment, and prevention.
Perspective:
Interestingly, very dense plaque is associated with reduced CV events, and CV risk factors including diabetes are inversely associated with plaque density, while statin use and physical activity are positively associated with plaque density. Lower risk for CVD associated with higher CAC density varies by level of volume. Rather than being used as a continuous volume, volume ≤130 mm3 may be the clinically useful cut point (Bhatia HS, et al., Circ Cardiovasc Imaging 2023;16:e014788). Additionally, when added to the ASCVD risk score, CAC volume and density provided the strongest prediction for CHD and CVD events, and the highest correct net reclassification including that by the Agatston score (Criqui MH, et al., JACC Cardiovasc Imaging 2017;10:845-54).
The clinical application of CAC density has yet to be defined. In the future, integrating common clinical CVD risk predictors from the new American Heart Association (AHA) PREVENT and adding biomarkers high-sensitivity C-reactive protein (hsCRP) and lipoprotein(a) [Lp(a)] and CAC density may provide a much more accurate CVD risk assessment—possibly for primary and secondary prevention—by helping to decide treatments and treatment intensity in clinical trials.
Clinical Topics: Noninvasive Imaging, Prevention
Keywords: Atherosclerosis, Computed Tomography, Plaque, Atherosclerotic
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