Calcium density in plaques, a predictor of future CV events, JAMA study.

Coronary calcium scoring by CT imaging has drawn attention over the past 2 decades as a method of risk stratification for primary prevention in intermediate disease risk category patients. However recent evidence indicates that it is not only the amount of calcium that predicts the future risk of cardiovascular events but perhaps more important is the density of calcium in the lipid plaques.

In this regard this month's JAMA Cardiology reports a study by Rosendael et al that suggests an association of statin use with greater rates of transformation of coronary atherosclerosis toward high-density calcium, thus supporting the concept of reduced atherosclerotic risk with increased densification of calcium.

The density of atherosclerotic plaque forms the basis for categorizing calcified and noncalcified morphology of plaques. Low-density calcium plaques have a higher risk of rupture than higher-density calcium, such as 1K (very dense calcium >1000 Hounsfield units [HU] plaques.

The present study aimed to assess whether alterations in plaque across a range of density measurements provide a more detailed understanding of atherosclerotic disease progression.

The authors enrolled 857 patients who underwent serial coronary computed tomography angiography 2 or more years apart and had quantitative measurements of coronary plaques throughout the entire coronary artery tree.

The main outcome was progression of plaque composition of individual coronary plaques. Six plaque composition types were defined on a voxel-level basis according to the plaque attenuation : low attenuation (−30 to 75 HU), fibro-fatty (76-130 HU), fibrous (131-350 HU), low-density calcium (351-700 HU), high-density calcium (701-1000 HU), and 1K (>1000 HU).

The progression rates of these 6 compositional plaque types were evaluated according to the interaction between statin use and baseline plaque volume, adjusted for risk factors and time interval between scans. Plaque progression was also examined based on baseline calcium density.

In this cohort study assessing serial coronary computed tomography angiographic images of 2458 coronary lesions among 857 patients:

1. Untreated coronary lesions progressed in volume for all 6 compositional plaque types whereas statin therapy was associated with decreases in low-attenuation and fibro-fatty plaque and with greater progression of high-density calcium and 1K plaque.

2. Statin therapy was not associated with a change in calcified plaque but with a transformation toward more dense calcium, which was associated with slower overall plaque progression.

"Our analysis provides insight into the magnitude and directionality of coronary atherosclerotic disease progression, including observations following intercurrent preventive therapy", noted the authors.

They observed a natural trend toward progression of both noncalcified and calcified plaque of atherosclerosis. This trend appeared to be modified in association with statin therapy to a decrease in LAP and fibro-fatty plaque volumes along with larger increases of high-density calcium and 1K plaque compared with plaques in patients not treated with statins.

These findings appear to be associated with a seesaw effect, whereby plaque transforms toward higher-density calcification. Specifically, statin therapy was not associated with overall calcified plaque progression but with a transformation toward denser calcium.

"Distinct differences in the overall plaque progression rates were observed according to calcium density, with the slowest progression for lesions with the densest calcium (1K plaque)", add the authors in discussion.

Spotty calcification (considered a high-risk plaque feature that has been associated with future ACS) was characterized by large volumes of noncalcified plaque and low-density calcification, but not by high-density calcification or 1K plaque. This less favorable plaque phenotype may explain its value in risk assessment but also highlights that any independent prognostic value of spotty calcification needs more study.

Source: JAMA Cardiology: doi:10.1001/jamacardio.2021.3055