Research Article| Volume 240, ISSUE 1, P205-211, May 2015

Effect of the local hemodynamic environment on the de novo development and progression of eccentric coronary atherosclerosis in humans: Insights from PREDICTION


      • ESS features (i.e. low magnitude and marked circum. heterogeneity) are associated with de novo eccentric plaque formation.
      • Worsening of plaque eccentricity in diseased regions presents in areas with both low ESS and large plaque burden.
      • The hemodynamic milieu is critical for eccentric coronary plaque formation in both early and advanced disease stages.



      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.


      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).


      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).


      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.


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        • Mohler 3rd, E.R.
        • Sarov-Blat L.
        • Shi Y.
        • Hamamdzic D.
        • Zalewski A.
        • Macphee C.
        • et al.
        Site-specific atherogenic gene expression correlates with subsequent variable lesion development in coronary and peripheral vasculature.
        Arterioscler. Thromb. Vasc. Biol. 2008 May; 28: 850-855
        • Box L.C.
        • Angiolillo D.J.
        • Suzuki N.
        • Box L.A.
        • Jiang J.
        • Guzman L.
        • et al.
        Heterogeneity of atherosclerotic plaque characteristics in human coronary artery disease: a three-dimensional intravascular ultrasound study.
        Catheter. Cardiovasc. Interv. 2007 Sep; 70: 349-356
        • Koskinas K.C.
        • Sukhova G.K.
        • Baker A.B.
        • Papafaklis M.I.
        • Chatzizisis Y.S.
        • Coskun A.U.
        • et al.
        Thin-capped atheromata with reduced collagen content in pigs develop in coronary arterial regions exposed to persistently low endothelial shear stress.
        Arterioscler. Thromb. Vasc. Biol. 2013 Jul; 33: 1494-1504
        • Yamagishi M.
        • Terashima M.
        • Awano K.
        • Kijima M.
        • Nakatani S.
        • Daikoku S.
        • et al.
        Morphology of vulnerable coronary plaque: insights from follow-up of patients examined by intravascular ultrasound before an acute coronary syndrome.
        J. Am. Coll. Cardiol. 2000 Jan; 35: 106-111
        • von Birgelen C.
        • Klinkhart W.
        • Mintz G.S.
        • Papatheodorou A.
        • Herrmann J.
        • Baumgart D.
        • et al.
        Plaque distribution and vascular remodeling of ruptured and nonruptured coronary plaques in the same vessel: an intravascular ultrasound study in vivo.
        J. Am. Coll. Cardiol. 2001 Jun 1; 37: 1864-1870
        • Sano K.
        • Kawasaki M.
        • Ishihara Y.
        • Okubo M.
        • Tsuchiya K.
        • Nishigaki K.
        • et al.
        Assessment of vulnerable plaques causing acute coronary syndrome using integrated backscatter intravascular ultrasound.
        J. Am. Coll. Cardiol. 2006 Feb 21; 47: 734-741
        • Caro C.G.
        Discovery of the role of wall shear in atherosclerosis.
        Arterioscler. Thromb. Vasc. Biol. 2009 Feb; 29: 158-161
        • Davies P.F.
        Hemodynamic shear stress and the endothelium in cardiovascular pathophysiology.
        Nat. Clin. Pract. Cardiovasc. Med. 2009 Jan; 6: 16-26
        • Wentzel J.J.
        • Chatzizisis Y.S.
        • Gijsen F.J.
        • Giannoglou G.D.
        • Feldman C.L.
        • Stone P.H.
        Endothelial shear stress in the evolution of coronary atherosclerotic plaque and vascular remodelling: current understanding and remaining questions.
        Cardiovasc. Res. 2012 Nov 1; 96: 234-243
        • Cheng C.
        • Tempel D.
        • van Haperen R.
        • van der Baan A.
        • Grosveld F.
        • Daemen M.J.
        • et al.
        Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress.
        Circulation. 2006 Jun 13; 113: 2744-2753
        • Chatzizisis Y.S.
        • Baker A.B.
        • Sukhova G.K.
        • Koskinas K.C.
        • Papafaklis M.I.
        • Beigel R.
        • et al.
        Augmented expression and activity of extracellular matrix-degrading enzymes in regions of low endothelial shear stress colocalize with coronary atheromata with thin fibrous caps in pigs.
        Circulation. 2011 Feb 15; 123: 621-630
        • Phinikaridou A.
        • Hua N.
        • Pham T.
        • Hamilton J.A.
        Regions of low endothelial shear stress colocalize with positive vascular remodeling and atherosclerotic plaque disruption: an in vivo magnetic resonance imaging study.
        Circ. Cardiovasc. Imaging. 2013 Mar 1; 6: 302-310
        • Stone P.H.
        • Saito S.
        • Takahashi S.
        • Makita Y.
        • Nakamura S.
        • Kawasaki T.
        • et al.
        Prediction of progression of coronary artery disease and clinical outcomes using vascular profiling of endothelial shear stress and arterial plaque characteristics: the PREDICTION study.
        Circulation. 2012 Jul 10; 126: 172-181
        • Feldman C.L.
        • Coskun A.U.
        • Yeghiazarians Y.
        • Kinlay S.
        • Wahle A.
        • Olszewski M.E.
        • et al.
        Remodeling characteristics of minimally diseased coronary arteries are consistent along the length of the artery.
        Am. J. Cardiol. 2006 Jan 1; 97: 13-16
        • Puri R.
        • Liew G.Y.
        • Nicholls S.J.
        • Nelson A.J.
        • Leong D.P.
        • Carbone A.
        • et al.
        Coronary beta2-adrenoreceptors mediate endothelium-dependent vasoreactivity in humans: novel insights from an in vivo intravascular ultrasound study.
        Eur. Heart J. 2012 Feb; 33: 495-504
        • Bayturan O.
        • Tuzcu E.M.
        • Nicholls S.J.
        • Balog C.
        • Lavoie A.
        • Uno K.
        • et al.
        Attenuated plaque at nonculprit lesions in patients enrolled in intravascular ultrasound atherosclerosis progression trials.
        J. Am. Coll. Cardiol. Interv. 2009 Jul; 2: 672-678
        • Mintz G.S.
        • Popma J.J.
        • Pichard A.D.
        • Kent K.M.
        • Satler L.F.
        • Chuang Y.C.
        • et al.
        Limitations of angiography in the assessment of plaque distribution in coronary artery disease: a systematic study of target lesion eccentricity in 1446 lesions.
        Circulation. 1996 Mar 1; 93: 924-931
        • Virmani R.
        • Burke A.P.
        • Kolodgie F.D.
        • Farb A.
        Pathology of the thin-cap fibroatheroma: a type of vulnerable plaque.
        J. Interv. Cardiol. 2003 Jun; 16: 267-272
        • Liu Y.S.
        • Hu X.B.
        • Li H.Z.
        • Jiang W.D.
        • Wang X.
        • Lin H.
        • et al.
        Association of lipoprotein-associated phospholipase A(2) with characteristics of vulnerable coronary atherosclerotic plaques.
        Yonsei Med. J. 2011 Nov; 52: 914-922
        • Chen W.Q.
        • Zhang L.
        • Liu Y.F.
        • Chen L.
        • Ji X.P.
        • Zhang M.
        • et al.
        Prediction of atherosclerotic plaque ruptures with high-frequency ultrasound imaging and serum inflammatory markers.
        Am. J. Physiol. Heart Circ. Physiol. 2007 Nov; 293: H2836-H2844
        • Ohara T.
        • Toyoda K.
        • Otsubo R.
        • Nagatsuka K.
        • Kubota Y.
        • Yasaka M.
        • et al.
        Eccentric stenosis of the carotid artery associated with ipsilateral cerebrovascular events.
        AJNR Am. J. Neuroradiol. 2008 Jun; 29: 1200-1203
        • Tardy Y.
        • Resnick N.
        • Nagel T.
        • Gimbrone Jr., M.A.
        • Dewey Jr., C.F.
        Shear stress gradients remodel endothelial monolayers in vitro via a cell proliferation-migration-loss cycle.
        Arterioscler. Thromb. Vasc. Biol. 1997 Nov; 17: 3102-3106
        • Buchanan J.R.
        • Kleinstreuer C.
        • Hyun S.
        • Truskey G.A.
        Hemodynamics simulation and identification of susceptible sites of atherosclerotic lesion formation in a model abdominal aorta.
        J. Biomech. 2003 Aug; 36: 1185-1196
        • Knight J.
        • Olgac U.
        • Saur S.C.
        • Poulikakos D.
        • Marshall Jr., W.
        • Cattin P.C.
        • et al.
        Choosing the optimal wall shear parameter for the prediction of plaque location-A patient-specific computational study in human right coronary arteries.
        Atherosclerosis. 2010 Aug; 211: 445-450
        • Suo J.
        • Ferrara D.E.
        • Sorescu D.
        • Guldberg R.E.
        • Taylor W.R.
        • Giddens D.P.
        Hemodynamic shear stresses in mouse aortas: implications for atherogenesis.
        Arterioscler. Thromb. Vasc. Biol. 2007 Feb; 27: 346-351
        • Bourantas C.V.
        • Papafaklis M.I.
        • Naka K.K.
        • Tsakanikas V.D.
        • Lysitsas D.N.
        • Alamgir F.M.
        • et al.
        Fusion of optical coherence tomography and coronary angiography – in vivo assessment of shear stress in plaque rupture.
        Int. J. Cardiol. 2012 Mar 8; 155: e24-e26
        • Fukumoto Y.
        • Hiro T.
        • Fujii T.
        • Hashimoto G.
        • Fujimura T.
        • Yamada J.
        • et al.
        Localized elevation of shear stress is related to coronary plaque rupture: a 3-dimensional intravascular ultrasound study with in-vivo color mapping of shear stress distribution.
        J. Am. Coll. Cardiol. 2008 Feb 12; 51: 645-650
        • Myers J.G.
        • Moore J.A.
        • Ojha M.
        • Johnston K.W.
        • Ethier C.R.
        Factors influencing blood flow patterns in the human right coronary artery.
        Ann. Biomed. Eng. 2001 Feb; 29: 109-120
        • Feldman C.L.
        • Ilegbusi O.J.
        • Hu Z.
        • Nesto R.
        • Waxman S.
        • Stone P.H.
        Determination of in vivo velocity and endothelial shear stress patterns with phasic flow in human coronary arteries: a methodology to predict progression of coronary atherosclerosis.
        Am. Heart J. 2002 Jun; 143: 931-939