High-intensity statin treatment is associated with reduced plaque structural stress and remodelling of artery geometry and plaque architecture

AIMS: Plaque structural stress (PSS) is a major cause of atherosclerotic plaque rupture and major adverse cardiovascular events (MACE). We examined the predictors of changes in peak and mean PSS (ΔPSS(peak), ΔPSS(mean)) in three studies of patients receiving either standard medical or high-intensity statin (HIS) treatment. METHODS AND RESULTS: We examined changes in PSS, plaque size, and composition between 7348 co-registered baseline and follow-up virtual-histology intravascular ultrasound images in patients receiving standard medical treatment (controls, n = 18) or HIS (atorvastatin 80 mg, n = 20, or rosuvastatin 40 mg, n = 22). The relationship between changes in PSS(peak) and plaque burden (PB) differed significantly between HIS and control groups (P < 0.001). Notably, PSS(peak) increased significantly in control lesions with PB >60% (P = 0.04), but not with HIS treatment. However, ΔPSS(peak) correlated poorly with changes in lumen and plaque area or PB, plaque composition, or lipid lowering. In contrast, ΔPSS(peak) correlated significantly with changes in lumen curvature, irregularity, and roughness (P < 0.05), all of which were reduced in HIS patients. ΔPSS(mean) correlated with changes in lumen area, PA, PB, and circumferential calcification, and was unchanged with either treatment. CONCLUSION: Our observational study shows that PSS(peak) changes over time were associated with baseline disease severity and treatment. The PSS(peak) increase seen in advanced lesions with standard treatment was associated with remodelling artery geometry and plaque architecture, but this was not seen after HIS treatment. Smoothing plaques by reducing plaque/lumen roughness, irregularity, and curvature represents a novel mechanism whereby HIS may reduce PSS and, thus may protect against plaque rupture and MACE.