Discordance Between Coronary Artery Calcium Area and Density Predicts Long-Term Atherosclerotic Cardiovascular Disease Risk

Background: Coronary artery calcium (CAC) is commonly quantified as the product of 2 generally correlated measures: plaque area and calcium density. Objectives: The authors sought to determine whether discordance between calcium area and density has long-term prognostic importance in atherosclerotic cardiovascular disease (ASCVD) risk. Methods: The authors studied 10,373 primary prevention participants from the CAC Consortium with CAC >0. Based on their median values, calcium area and mean calcium density were divided into 4 mutually exclusive concordant/discordant groups. Cox proportional hazards regression assessed the association of calcium area/density groups with ASCVD mortality over a median of 11.7 years, adjusting for traditional risk factors and the Agatston CAC score. Results: The mean age was 56.7 years, and 24% were female. The prevalence of plaque discordance was 19% (9% low calcium area/high calcium density, 10% high calcium area/low calcium density). Female sex (odds ratio [OR]: 1.48 [95% CI: 1.27-1.74]) and body mass index (OR: 0.81 [95% CI: 0.76-0.87], per 5 kg/m² higher) were significantly associated with high calcium density discordance, whereas diabetes (OR: 2.23 [95% CI: 1.85-3.19]) was most strongly associated with discordantly low calcium density. Compared to those with low calcium area/low calcium density, individuals with low calcium area/high calcium density had a 71% lower risk of ASCVD death (HR: 0.29 [95% CI: 0.09-0.95]). Conclusions: For a given CAC score, high calcium density relative to plaque area confers lower long-term ASCVD risk, likely serving as an imaging marker of biological resilience for lesion vulnerability. Additional research is needed to define a robust definition of calcium area/density discordance for routine clinical risk prediction.