Systematic Review of Biomechanical Forces Associated with Carotid Plaque Disruption and Stroke.

Abstract

Objective: Carotid plaque disruption with release of atheroembolic debris and consequent brain infarction is the primary mechanism for brain injury in patients with carotid stenosis. Disease severity is traditionally quantified by the degree of stenosis, though it is not an accurate marker of stroke-risk. It has been proposed that biomechanical forces acting on a carotid plaque may render it vulnerable to rupture by causing adverse remodeling of its morphology, or by direct disruption. We conducted a systematic review to assess the forces acting on carotid plaques and their relationship to adverse plaque outcomes.

Methods: A literature search for studies reporting measurements of flow-related biomechanical forces acting on carotid atherosclerotic plaques was conducted using PubMed, Embase and Web of Science. Studies were included if they reported on human carotid plaques, used patient-specific geometry, measured forces on or in the atherosclerotic lesions, and reported on carotid plaque-related adverse outcomes.

Results: Of 5,635 manuscripts screened, 154 met eligibility criteria. Forces were computed using patient-specific arterial geometry derived from multiple imaging modalities, mainly magnetic resonance imaging (58.4%) and ultrasonography (25.3%). Methodologies used to quantify the forces included computational fluid dynamics (31.8%), finite element analysis (10.4%), fluid-structure interaction models (27.3%), in-vivo measurements (29.9%), or in-vitro assessments (0.6%). Wall shear stress (WSS) and plaque wall stress (PWS) were the most frequently measured forces, in 72.1% and 45.5% of studies respectively. Principal PWS (n=15 studies) and WSS (n=21 studies) were elevated in patients with adverse outcomes. PWS levels of >160 kPa had a sensitivity of >80% and specificity of >75% in identifying patients with adverse events. Increasing PWS was associated with subsequent ischemic cerebrovascular events (HR=12.98 per 1 kPa increase, p=0.02). WSS levels of >50 dyn/cm2 had a sensitivity of 100% and specificity of 67% in differentiating patients with adverse events (plaque rupture, cerebral infarction, stroke, or transient ischemic attack) compared to those without.

Conclusions: There is heterogeneity in sample size, study design, imaging protocols, image-processing methodology, forces assessed, and adverse carotid plaque-related outcomes measured in the literature. Despite these limitations, increasing PWS and WSS were consistently associated with adverse plaque outcomes, and predicted adverse outcomes with moderate to high degrees of sensitivity and specificity. Since the information available is heterogenous, these relationships need to be confirmed in larger prospective studies.