Plaque Structural Stress: Detection, Determinants and Role in Atherosclerotic Plaque Rupture and Progression

Abstract

Atherosclerosis remains a major cause of death worldwide, with most myocardial infarctions being due to rupture or erosion of coronary plaques. Although several imaging modalities can identify features that confer risk, major adverse cardiovascular event (MACE) rates attributable to each plaque are low, such that additional biomarkers are required to improve risk stratification at plaque and patient level. Coronary arteries are exposed to continual mechanical forces, and plaque rupture occurs when plaque structural stress (PSS) exceeds its mechanical strength. Prospective studies have shown that peak PSS is correlated with acute coronary syndrome (ACS) presentation, plaque rupture, and MACE, and provides additional prognostic information to imaging. In addition, PSS incorporates multiple variables, including plaque architecture, plaque material properties, and haemodynamic data into a defined solution, providing a more detailed overview of higher-risk lesions. We review the methods for calculation and determinants of PSS, imaging modalities used for modeling PSS, and idealized models that explore structural and geometric components that affect PSS. We also discuss current experimental and clinical data linking PSS to the natural history of coronary artery disease, and explore potential for refining treatment options and predicting future events.

Keywords: atherosclerosis; computational modeling; intravascular imaging; plaque rupture; plaque structural stress.

Figure 1

Modeling of plaque structural stress. (A) The law of Laplace describes the relationship between transmural pressure (P) and wall tension (T). In a (cylindrical) blood vessel, there is a simple relationship between pressure and circumferential wall tension/stress. The law gives the average tension over the wall, but holds only for simple geometries. h = wall thickness; r = radius. Example of steps involved in computational modeling to calculate plaque structural stress (PSS): (B) Suitable images (e.g., virtual histology intravascular ultrasound, VH-IVUS) showing plaque structure and components generated from in vivo or ex vivo studies; (C,D) Images undergo segmentation and meshing process; (E) Plaque material properties are obtained from ex vivo tensile testing of plaque components; (F) Finite element analysis (FEA) utilizes plaque geometry, structure, components, material properties, and haemodynamic conditions to generate a numerical solution of PSS. Adapted from Brown et al. (16).