Extension of increased atherosclerotic wall thickness into high shear stress regions is associated with loss of compensatory remodeling

Abstract

Background - Atherosclerosis preferentially develops at average low shear stress (SS) locations. SS-related signaling maintains lumen dimensions by inducing outward arterial remodeling. Prolonged plaque accumulation at low SS predilection locations explains an inverse relation between wall thickness (WT) and SS. No data exist on WT-SS relations when lumen narrowing and loss of compensatory remodeling commence. Methods and Results - In 14 patients, an angiographically normal artery (stenosis <50%) was investigated with ANGiography and ivUS (ANGUS) to provide 3D lumen and wall geometry. Selection of segments >5 mm in length, in between side branches, yielded 25 segments in 12 patients. SS at the wall was calculated by computational fluid dynamics. WT smaller than 0.2*lumen diameter was defined as normal. Largest arc of normal WT defined reference cross sections. Lumen area relative to the reference cross sections defined area stenosis (AS). Average segmental AS smaller or greater than 10% defined preserved or narrowed lumen, respectively. Total vessel area relative to the reference defined vascular remodeling (VR). For the preserved lumens (n = 11, AS = 1.7±5.6%, P = NS), axially averaged WT and SS were inversely related (slope, -0.46±0.55 mm/Pa, P < 0.05) and VR was positive (7±9%, P < 0.05). Narrowed segments (n = 13, 1 excluded, AS = 18±6%, P < 0.05) showed no relation between WT and SS or vascular remodeling. Conclusions - In patient coronary arteries, the often-reported inverse WT-SS relationship appears restricted to lumen preservation and positive vascular remodeling. Its disappearance with lumen narrowing suggests a growing importance of non-SS-related plaque progression.