Calcium Density as a Marker of Coronary Plaque Stabilization in Primary Prevention: The CAUGHT-CAD Trial

BACKGROUND: Despite primary prevention statin treatment, a substantial proportion of individuals remain at residual risk for cardiovascular events. Coronary computed tomographic angiography (CTA) enables the quantification of compositional changes in calcified plaque. OBJECTIVES: The aim of this study was to examine whether increases in coronary calcified plaque volume and density associated with statin therapy could be used as a marker of plaque stabilization in asymptomatic individuals undergoing serial coronary CTA. METHODS: In the CAUGHT-CAD trial, asymptomatic, statin-naive, intermediate-risk individuals were randomized to a primary prevention strategy (including statin treatment) vs usual care. Participants underwent coronary CTA at baseline and 3 years. In this post hoc analysis, volumes of 5 plaque subtypes were quantified: noncalcified (≤350 HU), low-density calcium (351-500 HU), intermediate-density calcium (501-700 HU), high-density calcium (701-1000 HU), and very high density calcium (>1,000 HU). The primary outcome was the per-lesion level change in volumes of calcified plaque subtypes. RESULTS: Eight hundred forty lesions were included from 338 participants (mean age: 58.3 ± 6.9 years, 57.1% men, 161 [47.6%] statin treated). Statin treatment was associated with greater progression in intermediate-density (β = 0.89, SE = 0.39; P = 0.02) and high-density (β = 0.79, SE = 0.24; P = 0.001) calcium, alongside regression of noncalcified plaque (β = -9.83, SE = 1.64; P < 0.001), following adjustment for cardiovascular risk factors, low-density lipoprotein cholesterol (LDL-C) level, and baseline plaque volume. Among statin-treated participants, LDL-C reduction ≥30% was associated with greater progression of high-density (β = 1.11, SE = 0.49; P = 0.03) and very high density (β = 1.68, SE = 0.85; P = 0.04) calcium. CONCLUSIONS: In asymptomatic, intermediate-risk individuals, statin treatment was associated with a shift toward higher density calcium within coronary plaques, most marked with effective lowering of LDL-C. (Coronary Artery Calcium Score: Use to Guide Management of Hereditary Coronary Artery Disease [CAUGHT-CAD]; ACTRN12614001294640).