Published Online
on July 14, 2003

A more recent version of this article appeared on July 29, 2003

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Submitted on December 5, 2002
Revised on April 22, 2003
Accepted on April 25, 2003

Effect of Endothelial Shear Stress on the Progression of Coronary Artery Disease, Vascular Remodeling, and In-Stent Restenosis in Humans. In Vivo 6-Month Follow-Up Study

Peter H. Stone MD^*, Ahmet U. Coskun PhD, Scott Kinlay MD, PhD, Maureen E. Clark MS, Milan Sonka PhD, Andreas Wahle PhD, Olusegun J. Ilegbusi PhD, Yerem Yeghiazarians MD, Jeffrey J. Popma MD, John Orav PhD, Richard E. Kuntz MD, MS, and Charles L. Feldman ScD

From the Cardiovascular Division, Brigham and Women's Hospital (P.H.S., S.K., M.E.C., Y.Y., J.J.P., J.O., R.E.K., C.L.F.), Boston, Mass; Department of Mechanical, Industrial, and Manufacturing Engineering, Northeastern University (A.U.C., O.J.I.), Boston, Mass; and Department of Electrical and Computer Engineering, The University of Iowa (M.S., A.W.), Iowa City.

^* To whom correspondence should be addressed. E-mail: pstone{at}partners.org.

Background--Native atherosclerosis and in-stent restenosis are focal and evolve independently. The endothelium controls local arterial responses by transduction of shear stress. Characterization of endothelial shear stress (ESS) may allow for prediction of progression of atherosclerosis and in-stent restenosis.

Methods and Results--By using intracoronary ultrasound, biplane coronary angiography, and measurement of coronary blood flow, we represented the artery in accurate 3D space and determined detailed characteristics of ESS and arterial wall/plaque morphology. Patients who underwent stent implantation and who had another artery with luminal obstruction <50% underwent intravascular profiling initially and after 6-month follow-up. Twelve arteries in 8 patients were studied: 6 native and 6 stented arteries. In native arteries, regions of abnormally low baseline ESS exhibited a significant increase in plaque thickness and enlargement of the outer vessel wall, such that lumen radius remained unchanged (outward remodeling). Regions of physiological ESS showed little change. Regions with increased ESS exhibited outward remodeling with normalization of ESS. In stented arteries, there was an increase in intima-medial thickness, a decrease in lumen radius, and an increase in ESS at all levels of baseline ESS.

Conclusions--The present study represents the first experience in humans relating ESS to subsequent outcomes in native and stented arteries. Regions of low ESS develop progressive atherosclerosis and outward remodeling, areas of physiological ESS remain quiescent, and areas of increased ESS exhibit outward remodeling. ESS may have a limited role in in-stent restenosis. This technology can predict areas of minor plaque likely to exhibit progression of atherosclerosis.

Key words: endothelium • atherosclerosis • coronary disease • shear stress

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