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(Circulation. 2008;117:993-1002.)
© 2008 American Heart Association, Inc.

Coronary Heart Disease

Prediction of the Localization of High-Risk Coronary Atherosclerotic Plaques on the Basis of Low Endothelial Shear Stress

An Intravascular Ultrasound and Histopathology Natural History Study

Yiannis S. Chatzizisis, MD, MSc^*; Michael Jonas, MD^*; Ahmet U. Coskun, PhD; Roy Beigel, MD; Benjamin V. Stone; Charles Maynard, PhD; Ross G. Gerrity, PhD; William Daley, MD; Campbell Rogers, MD; Elazer R. Edelman, MD, PhD; Charles L. Feldman, ScD; Peter H. Stone, MD

From the Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (Y.S.C., E.R.E., C.L.F., P.H.S.); Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Mass (Y.S.C., M.J., R.B., B.V.S., E.R.E.); Mechanical and Industrial Engineering, Northeastern University, Boston, Mass (A.U.C.); Department of Health Services, University of Washington, Seattle (C.M.); Department of Pathology, Medical College of Georgia, Augusta (R.G.G.); Novartis Pharmaceuticals Inc, East Hanover, NJ (W.D.); and Cordis Inc, Warren, NJ (C.R.).

Correspondence to Peter H. Stone, MD, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115. E-mail pstone{at}partners.org

Received February 7, 2007; accepted December 7, 2007.

Background— Low endothelial shear stress (ESS) promotes the development of atherosclerosis; however, its role in the progression of atherosclerotic plaques and evolution to inflamed high-risk plaques has not been studied. Our hypothesis was that the lowest values of ESS are responsible for the development of high-risk coronary atherosclerotic plaques associated with excessive expansive remodeling.

Methods and Results— Twenty-four swine, treated with streptozotocin to induce diabetes and fed a high-fat diet, were allocated into early (n=12) and late (n=12) atherosclerosis groups. Intima-media thickness was assessed by intravascular ultrasound in the coronary arteries at weeks 4 and 8 in the early group and weeks 23 and 30 in the late group. Plaques started to develop after week 8, leading to marked heterogeneity in plaque severity at week 30. ESS was calculated in plaque-free subsegments of interest (n=142) in the late group at week 23. Coronary arteries (n=31) of this group were harvested at week 30, and the subsegments of interest were identified and analyzed histopathologically. Low ESS was an independent predictor of the development of high-risk plaques, characterized by intense lipid accumulation, inflammation, thin fibrous cap, severe internal elastic lamina degradation, and excessive expansive remodeling. The severity of high-risk plaque characteristics at week 30 was significantly correlated with the magnitude of low ESS at week 23.

Conclusions— The magnitude of low ESS determines the complexity and heterogeneity of atherosclerotic lesions and predicts the development of high-risk plaque.

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