Abstract Body (Do not enter title and authors here): Background: Coronary artery calcium (CAC) is usually quantified by Agatston score, integrating both its density and area. Importantly, several studies have reported different prognostic implications between calcium density and volume, with the former inversely associated with cardiovascular disease (CVD) events suggesting predominantly “stable/healed” plaque and the latter better representation of total plaque burden. However, those studies predominantly involved middle-aged populations, with limited data on very older adults, and used estimated CAC density.

Aim: To examine the independent association of directly measured CAC density and volume with incident CVD events among the 75-and-older population.

Methods: We included 1,456 participants aged >75 from ARIC visit 7 (2018-2019) with CAC data (mean age 80.4 [SD 4.2] years, 58.2% female, 18.2% Black). We assessed CAC maximum peak density (the highest density across all calcified plaque[s] in each participant) and volume. We ran multivariable Cox models with composite CVD (myocardial infarction, stroke, and heart failure) as the outcome. Mean peak CAC density(the average of the highest HU in every plaque in each participant) were used to check the pattern consistency.

Results: During a median follow-up of 2.9 years, there were 122 CVD events. After adjusting for traditional CVD risk factors, both CAC density and volume were positively associated with CVD (e.g., hazard ratio for the highest (Q4) vs. the lowest (Q1) quartile 3.73 [95%CI 2.02-6.90] and 4.33 [2.44-7.66], respectively) (Model 1 in Table). When we further adjusted for each other, the associations were attenuated but remained significant (Model 2 in Table). The patterns were largely similar when we explored mean peak density.

Conclusions: Unlike results in previous studies with middle-aged adults and estimated CAC density, both directly measured CAC density and volume were positively and independently associated with increased CVD risk in the 75-and-older population.