title: Effect of the local hemodynamic environment on the de novo development and progression of eccentric coronary atherosclerosis in humans: insights from PREDICTION.
abstract: BACKGROUND
  Eccentric distribution of atheroma has been associated with plaques likely to rupture and cause an acute coronary syndrome, but the factors responsible for the development of eccentricity remain unknown. Endothelial shear stress (ESS) drives plaque formation. We aimed to investigate the role of the local ESS characteristics in the de novo development and progressive worsening of plaque eccentricity in humans.
  
  
  METHODS
  Vascular profiling (3-vessel 3D coronary reconstruction by angiography/intravascular ultrasound, and blood flow simulation for ESS computation) was performed in 374 patients at baseline & 6-10 months follow-up. At baseline, we identified (i) disease-free segments (n=2157), and (ii) diseased regions of luminal obstructions (n=408).
  
  
  RESULTS
  In disease-free regions, baseline low ESS magnitude (p<0.001), marked ESS circumferential heterogeneity (p=0.001), and their interaction (p=0.026) were associated with an increased probability of de novo eccentric plaque formation at follow-up. In diseased regions, baseline low ESS (odds ratio [OR]: 2.33, p=0.003) and large plaque burden (OR: 2.46, p=0.002) were independent predictors of substantially increasing plaque eccentricity index with worsening lumen encroachment. This combined outcome was more frequent in obstructions with both features vs. all others (33 vs. 12%; p<0.001). The incidence of percutaneous coronary intervention in worsening obstructions with increasing plaque eccentricity was higher (13.3 vs. 4.3%, p=0.011).
  
  
  CONCLUSIONS
  The local hemodynamic environment has a critical effect on the development of eccentric coronary plaques at both an early and advanced stage of atherosclerosis. Local ESS assessment could help in predicting sites prone to plaque disruption and acute coronary syndromes in humans.
authors: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Michail I
authors: MI
authors: Papafaklis
authors: Shonan Kamakura General Hospital, Kamakura, Japan.
authors: Saeko
authors: S
authors: Takahashi
authors: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Antonios P
authors: AP
authors: Antoniadis
authors: Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA.
authors: Ahmet U
authors: AU
authors: Coskun
authors: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Masaya
authors: M
authors: Tsuda
authors: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Shingo
authors: S
authors: Mizuno
authors: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Ioannis
authors: I
authors: Andreou
authors: Kyoto Katsura Hospital, Kyoto, Japan.
authors: Shigeru
authors: S
authors: Nakamura
authors: Hakodate Municipal Hospital, Hakodate, Japan.
authors: Yasuhiro
authors: Y
authors: Makita
authors: Sakakibara Heart Institute of Okayama, Okayama, Japan.
authors: Atsushi
authors: A
authors: Hirohata
authors: Shonan Kamakura General Hospital, Kamakura, Japan.
authors: Shigeru
authors: S
authors: Saito
authors: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Charles L
authors: CL
authors: Feldman
authors: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: pstone@partners.org.
authors: Peter H
authors: PH
authors: Stone
mesh_terms: D054058:Acute Coronary Syndrome / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D000368:Aged; D001783:Blood Flow Velocity; D017023:Coronary Angiography / Q000379:methods; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology*; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D012039:Regional Blood Flow; D012307:Risk Factors; D012422:Rupture, Spontaneous; D013312:Stress, Physiological; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D018084:Ultrasonography, Interventional
keywords: Atherosclerosis; Coronary artery disease; Endothelial shear stress; Natural history; Plaque eccentricity; Vulnerable plaque