Abstract Body (Do not enter title and authors here): Background: There is residual risk of atherosclerotic cardiovascular disease (ASCVD) that remains despite adequate risk factor (RF) control. Coronary artery calcium (CAC) has demonstrated value in ASCVD risk stratification. We evaluated the value of CAC in identifying residual risk of ASCVD events among those with traditional RF control.

Methods: Participants without clinical ASCVD were pooled from the Multi-Ethnic Study of Atherosclerosis, Heinz Nixdorf Recall Study, Framingham Heart Study, and Jackson Heart Study. RF control was classified as “guideline-concordant” and “optimal” (Figure 1). Participants were stratified by the number of controlled RFs at baseline and CAC score (CAC = 0, 1-99, ≥100). Cox proportional hazards models examined the association between CAC and incident ASCVD events.

Results: The study included 14,780 individuals (mean age 58 years (SD: 11), 54% female, 59% White, 27% Black, 50% CAC = 0). Over a median follow-up of 14.6 years, there were 1,441 incident ASCVD events. The distribution of CAC and ASCVD event incidence is shown in Panel A; 10% of those with 3 optimal RFs and 19% of those with 3 guideline-concordant RFs controlled had CAC > 100. The rate of ASCVD events decreased with more RFs controlled and increased with higher CAC. Overall, optimal RF control was associated with lower ASCVD event rates compared to guideline-concordant control. At every level of RF control, CAC > 100 was associated with increased HRs for incident ASCVD (Panel B). Those with CAC ≥ 100 and controlled RFs experienced ASCVD rates numerically comparable to or exceeding those with uncontrolled RFs but CAC = 0 (Panel A). Adjusted HR (95% CI) for ASCVD events with CAC > 100 compared to CAC = 0 was 5.0 (2.0, 12.9) in optimal RF control and 3.7 (2.6, 5.4) in guideline-concordant RF control.

Conclusion: There is significant heterogeneity in residual ASCVD risk among those with optimal or guideline-concordant traditional RF control and CAC can help identify this risk. Irrespective of RF control, a higher CAC burden was associated with increased ASCVD risk. Future studies could use CAC testing to identify those with higher residual ASCVD risk despite effective traditional RF control to target for novel therapies.