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

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.

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.

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.

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.

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).