Statins reduce Atherosclerotic risk by increasing densification of Plaques: JAMA

Previous studies have shown that increasing calcium density was associated with slower overall plaque progression. Based on previous study findings the authors wrote, "Low-density calcium may not portend the same low-risk status as higher-density calcium, such as 1K plaque." To further examine, Dr Alexander van Rosendael and his team conducted a study PARADIGM, to assess whether alterations in plaque across a range of density measurements provide a more detailed understanding of atherosclerotic disease progression.

PARADIGM was conducted from 2013 to 2016 at 13 sites in 7 countries. The researchers included a total of 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 major outcome assessed was a progression of plaque composition of individual coronary plaques. They categorized plaques into the following six types according to attenuation (expressed in Hounsfield units [HU]):

1. Low attenuation (-30 to 75 HU)

2. Fibro-fatty (76 HU to 130 HU)

3. Fibrous (131 HU to 350 HU)

4. Low-density calcium (351 HU to 700 HU)

5. High-density calcium (701 HU to 1,000 HU)

6. 1K (> 1,000 HU)

They assessed 2,458 coronary lesions, over two-thirds of which were in patients treated with statins. They evaluated the plaque progression rates of these 6 compositional plaque types according to the interaction between statin use, baseline plaque volume and calcium density.

Key findings of the study were:

• Upon analysis, the researchers found that untreated coronary lesions increased in volume over time for all 6 compositional types.
• They also found that statin therapy was associated with

◊ Decreased volume in low-attenuation plaque (β, −0.02)

◊ Fibro-fatty plaque (β, −0.03)

◊ Greater progression of high-density calcium plaque (β, 0.02) and

◊ 1K plaque (β, 0.02).

• When analyses were restricted to lesions without low-attenuation plaque or fibro-fatty plaque at baseline, they noted that statin therapy was not associated with a change in overall calcified plaque volume (β, −0.03) but was associated with a transformation toward more dense calcium.
• Upon interaction analysis between baseline plaque volume and calcium density, they found that more dense coronary calcium was associated with less plaque progression.

The authors concluded, "The results suggest an association of statin use with greater rates of transformation of coronary atherosclerosis toward high-density calcium. A pattern of slower overall plaque progression was observed with increasing density. All findings support the concept of reduced atherosclerotic risk with increased densification of calcium."

For further information:

DOI:10.1001/jamacardio.2021.3055