Morphology (PREDICTION) Study were to determine the role of local hemodynamic and vascular characteristics in coronary plaque progression and to relate plaque changes to clinical events. Methods and Results-Vascular profiling, using coronary angiography and intravascular ultrasound, was used to reconstruct each artery and calculate endothelial shear stress and plaque/remodeling characteristics in vivo. Three-vessel vascular profiling (2.7 arteries per patient) was performed at baseline in 506 patients with an acute coronary syndrome treated with a percutaneous coronary intervention and in a subset of 374 (74%) consecutive patients 6 to 10 months later to assess plaque natural history. Each reconstructed artery was divided into sequential 3-mm segments for serial analysis. One-year clinical follow-up was completed in 99.2%. Symptomatic clinical events were infrequent: only 1 (0.2%) cardiac death; 4 (0.8%) patients with new acute coronary syndrome in nonstented segments; and 15 (3.0%) patients hospitalized for stable angina. Increase in plaque area (primary end point) was predicted by baseline large plaque burden; decrease in lumen area (secondary end point) was independently predicted by baseline large plaque burden and low endothelial shear stress. Large plaque size and low endothelial shear stress independently predicted the exploratory end points of increased plaque burden and worsening of clinically relevant luminal obstructions treated with a percutaneous coronary intervention at follow-up. The combination of independent baseline predictors had a 41% positive and 92% negative predictive value to predict progression of an obstruction treated with a percutaneous coronary intervention. Conclusions-Large plaque burden and low local endothelial shear stress provide independent and additive prediction to identify plaques that develop progressive enlargement and lumen narrowing. Clinical Trial Registration-URL: http:www.//clinicaltrials.gov. Unique Identifier: NCT01316159. (Circulation. 2012;126:172-181.) Key Words: atherosclerosis Ⅲ endothelium Ⅲ natural history Ⅲ shear stress A therosclerosis is a systemic disease with focal and eccentric manifestations. 1 In a patient with coronary artery disease (CAD) and systemic risk factors, each coronary lesion progresses, regresses, or remains quiescent in an independent manner, 2 indicating that local vascular factors must be a major determinant responsible for the behavior of individual plaques. Editorial see p 161 Clinical Perspective on p 181The vascular endothelium is in a unique and pivotal position to respond to the extremely dynamic forces acting on the vessel wall because of the complex 3-dimensional (3D) Received January 27, 2012; accepted May 16, 2012. Identification of an early coronary atherosclerotic plaque likely to acquire high-risk characteristics and precipitate a new coronary event may allow for development of preemptive strategies to avert adverse events. The recent Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PR...

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