Conventional coronary artery calcium (CAC) scoring may not fully capture lower-density calcification linked to vulnerable atherosclerotic plaque. A study published in the European Journal of Preventive Cardiology developed a vulnerable calcium index (VCI) to quantify sub-Agatston CAC burden and evaluated its association with major adverse cardiovascular events (MACE) and high-risk plaque (HRP) features.

The analysis included 1,837 asymptomatic participants from the CLARIFY CT calcium score registry and 1,075 patients from the SCOT-HEART trial presenting to chest pain clinics. Multivariable analyses adjusted for cardiovascular risk factors, baseline statin use, and Agatston score. Associations between VCI and coronary CT angiography (CCTA)-defined HRP features were also evaluated in SCOT-HEART participants with paired CT calcium score and CCTA imaging.

Findings

• Median follow-up was 4.8 years in CLARIFY and 4.9 years in SCOT-HEART.
• Higher VCI independently corresponded with increased MACE risk in both cohorts (adjusted HR 1.12; 95% CI 1.02–1.22; p = 0.02 and adjusted HR 1.16; 95% CI 1.03–1.31; p = 0.02, respectively).
• Participants in the highest quartile of adjusted model risk showed substantially higher event rates than those in the lowest quartile (CLARIFY HR 25.0; SCOT-HEART HR 33.7; p < 0.005 for both).
• Adding VCI to Agatston score improved C-index for MACE prediction from 0.62 to 0.66 in CLARIFY and from 0.72 to 0.75 in SCOT-HEART (p < 0.001 for both).
• VCI also improved net reclassification beyond Agatston score in both cohorts (CLARIFY 0.52 [95% CI 0.40–0.64]; SCOT-HEART 0.72 [95% CI 0.48–0.94]; p < 0.005 for both).
• In SCOT-HEART, higher VCI values corresponded with all assessed CCTA-defined HRP features, with ORs ranging from 1.45 to 1.85 (p < 0.001 for all).

The findings suggest that sub-Agatston CAC burden captured by VCI corresponded with both adverse cardiovascular outcomes and vulnerable plaque characteristics. Incorporating VCI into CAC reporting may improve cardiovascular risk stratification beyond conventional Agatston scoring.