Abstract 255: Low Endothelial Shear Stress (ESS) is Responsible for the Heterogeneity and Severity of Coronary Atherosclerotic Plaques: An In-Vivo IVUS Natural History Study
Objectives: Atherosclerotic lesions are multifocal and progress at different rates, despite exposure to the same systemic risk factors. We investigated the potential role of focal areas of low ESS on the localization and severity of plaque formation.
Methods: Twenty seven streptozotocin-induced diabetic hyperlipidemic swine were studied. Serial IVUS with 3D reconstruction of each coronary artery was performed at 4, 8, 23 and 30 wks. Plaque severity by IVUS was defined by plaque thickness (0.4 – 0.7 mm vs 0.8 –1.0 mm vs >1.0 mm). Local ESS throughout each artery was determined from computational fluid dynamics. Plaque-free subsegments by IVUS (average length 5 mm) with low (<1.2 Pa), moderate (1.2–2.4 Pa) and high (>2.4 Pa) ESS were identified in each artery at 23 wks; and assessed by histology at 30 wks. Plaque severity by histology was defined by intimal/media ratio and maximum intimal thickness.
Results: Plaque developed and progressed after 8 weeks, with remarkable heterogeneity of number and severity of plaque by IVUS over time (Fig A⇓). Histology indicated that subsegments (n=43, average=4.2 per artery) with low ESS at baseline were associated with significantly higher intima/media ratio and maximum intimal thickness at follow-up compared to areas with moderate or high ESS (p<0.01, Fig B⇓). Plaques in areas of low ESS were also all eccentric.
Conclusions: Low ESS determines the location and severity of coronary artery plaque. The heterogeneity of the natural history of atherosclerotic plaques is related to the local ESS environment. Ongoing analyses focus on the role of local ESS on vascular remodeling, plaque inflammation and neovascularization over time.