Coronary Heart Disease Coronary Artery Wall Shear Stress Is Associated With Progression and Transformation of Atherosclerotic Plaque and Arterial Remodeling in Patients With Coronary Artery Disease

Background—Experimental studies suggest that low wall shear stress (WSS) promotes plaque development and high WSS is associated with plaque destabilization. We hypothesized that low-WSS segments in patients with coronary artery disease develop plaque progression and high-WSS segments develop necrotic core progression with fibrous tissue regression. Methods and Results—Twenty patients with coronary artery disease underwent baseline and 6-month radiofrequency intravascular ultrasound (virtual histology intravascular ultrasound) and computational fluid dynamics modeling for WSS calculation. For each virtual histology intravascular ultrasound segment (nϭ2249), changes in plaque area, virtual histology intravascular ultrasound– derived plaque composition, and remodeling were compared in low-, intermediate-, and high-WSS categories. Compared with intermediate-WSS segments, low-WSS segments developed progression of plaque area (Pϭ0.027) and necrotic core (PϽ0.001), whereas high-WSS segments had progression of necrotic core (PϽ0.001) and dense calcium (PϽ0.001) and regression of fibrous (PϽ0.001) and fibrofatty (PϽ0.001) tissue. Compared with intermediate-WSS segments, low-WSS segments demonstrated greater reduction in vessel (PϽ0.001) and lumen area (PϽ0.001), and high-WSS segments demonstrated an increase in vessel (PϽ0.001) and lumen (PϽ0.001) area. These changes resulted in a trend toward more constrictive remodeling in low-compared with high-WSS segments (73% versus 30%; Pϭ0.06) and more excessive expansive remodeling in high-compared with low-WSS segments (42% versus 15%; Pϭ0.16). Conclusions—Compared with intermediate-WSS coronary segments, low-WSS segments develop greater plaque and necrotic core progression and constrictive remodeling, and high-WSS segments develop greater necrotic core and calcium progression, regression of fibrous and fibrofatty tissue, and excessive expansive remodeling, suggestive of transformation to a more vulnerable phenotype. A lthough cardiovascular risk factors lead to systemic inflammation, oxidative stress, and endothelial dysfunc-tion, it is recognized that coronary atherosclerotic plaques are focally distributed with highly variable rates of progression. However, prediction of regional plaque progression in an individual coronary segment remains elusive. Alterations in wall shear stress (WSS) have been implicated in the focal distribution and pathophysiology of coronary atherosclerosis. 1–5 Low WSS leads to a proatherogenic endothelial cell phenotype 1–3 and focal development of ath-erosclerosis and vascular remodeling in experimental models 6 – 8 and pilot clinical studies. 9,10 Both low WSS and high WSS have been implicated in the production of matrix metalloproteinases and plasmin by endothelial cells that can destabilize plaque fibrous caps. 11–13 In addition, high WSS has been shown to induce apoptosis of smooth muscle cells, 14,15 which might enhance plaque vulnerability. To date, the role of both low WSS and high WSS in the development of plaque …