Combination of plaque burden, wall shear stress, and plaque phenotype has incremental value for prediction of coronary atherosclerotic plaque progression and vulnerability.

AIMS Large plaque burden, certain phenotypes, and low wall shear stress (WSS) are associated with adverse outcomes and high WSS with development of plaque vulnerability. We aimed to investigate the incremental value of the combination of plaque burden, WSS and plaque phenotype for prediction of coronary atherosclerotic plaque progression and vulnerability. METHODS Twenty patients with CAD underwent baseline and 6-month follow-up coronary virtual histology-intravascular ultrasound (VH-IVUS) and computational fluid dynamics modeling for calculation of WSS. Low WSS was defined as <10 dynes/cm(2) and high WSS as ≥25 dynes/cm(2). Baseline plaque characteristics and WSS were related to plaque progression and vulnerability. RESULTS In 2249 VH-IVUS frames analyzed, coronary segments with both plaque burden >40% and low WSS had significantly greater change in plaque area at follow-up (+0.68 ± 1.05 mm(2)), compared to segments with plaque burden >40% without low WSS (-0.28 ± 1.32 mm(2)) or segments with low WSS and plaque burden ≤40% (+0.05 ± 0.71 mm(2)) (p = 0.047). Among plaque phenotypes, pathologic intimal thickening (PIT) had the greatest increase in necrotic core (NC) area (p = 0.06) and greatest decrease in fibro-fatty (FF) area (p < 0.0001). At follow-up, compared to segments with either plaque burden >60%, PIT, or high WSS, those with a combination of plaque burden >60%, PIT, and high WSS developed greater increase in NC area (p = 0.002), greater decrease in FF (p = 0.004) and fibrous areas (p < 0.0001), and higher frequency of expansive remodeling (p = 0.019). CONCLUSION Combination of plaque burden, WSS, and plaque phenotype has incremental value for prediction of coronary plaque progression and increased plaque vulnerability in patients with non-obstructive CAD.

[1]  E. Edelman,et al.  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 , 2008, Circulation.

[2]  Patrick W Serruys,et al.  Tissue characterisation using intravascular radiofrequency data analysis: recommendations for acquisition, analysis, interpretation and reporting. , 2009, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[3]  S. Berceli,et al.  Increased Plasmin and Serine Proteinase Activity During Flow-Induced Intimal Atrophy in Baboon PTFE Grafts , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[4]  Michael Jonas,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 , 2011, Circulation.

[5]  D. Gordon,et al.  Nitric oxide-generating compounds inhibit total protein and collagen synthesis in cultured vascular smooth muscle cells. , 1995, Circulation research.

[6]  R. Virmani,et al.  Accuracy of in vivo coronary plaque morphology assessment: a validation study of in vivo virtual histology compared with in vitro histopathology. , 2006, Journal of the American College of Cardiology.

[7]  G. Garcı́a-Cardeña,et al.  Endothelial Dysfunction, Hemodynamic Forces, and Atherogenesis a , 2000, Annals of the New York Academy of Sciences.

[8]  E. Tuzcu,et al.  Coronary Plaque Classification With Intravascular Ultrasound Radiofrequency Data Analysis , 2002, Circulation.

[9]  S. Alper,et al.  Hemodynamic shear stress and its role in atherosclerosis. , 1999, JAMA.

[10]  H. Lijnen Plasmin and Matrix Metalloproteinases in Vascular Remodeling , 2001, Thrombosis and Haemostasis.

[11]  Michael C. McDaniel,et al.  Coronary Artery Wall Shear Stress Is Associated With Progression and Transformation of Atherosclerotic Plaque and Arterial Remodeling in Patients With Coronary Artery Disease , 2011, Circulation.

[12]  Michail I. Papafaklis,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 , 2012, Circulation.

[13]  B. Chen,et al.  Shear Stress Activation of SREBP1 in Endothelial Cells Is Mediated by Integrins , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[14]  C. Tracy,et al.  American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. , 2001, Journal of the American College of Cardiology.

[15]  P. Casey,et al.  The effect of combined arterial hemodynamics on saphenous venous endothelial nitric oxide production. , 2001, Journal of vascular surgery.

[16]  Habib Samady,et al.  Shear stress and plaque development , 2010, Expert review of cardiovascular therapy.

[17]  P. Serruys,et al.  Clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound regression/progression studies. , 2011, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[18]  Michael C. McDaniel,et al.  Effect of intensive atorvastatin therapy on coronary atherosclerosis progression, composition, arterial remodeling, and microvascular function. , 2012, The Journal of invasive cardiology.

[19]  Akiko Maehara,et al.  A prospective natural-history study of coronary atherosclerosis. , 2011, The New England journal of medicine.

[20]  Gary S. Mintz,et al.  The dynamic nature of coronary artery lesion morphology assessed by serial virtual histology intravascular ultrasound tissue characterization. , 2010, Journal of the American College of Cardiology.

[21]  E. Boerwinkle,et al.  From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. , 2003, Circulation.

[22]  A. Wahle,et al.  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 , 2003, Circulation.

[23]  J. Goldstein,et al.  The SREBP Pathway: Regulation of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Transcription Factor , 1997, Cell.

[24]  D. Vince,et al.  Automated coronary plaque characterisation with intravascular ultrasound backscatter: ex vivo validation. , 2007, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[25]  Habib Samady,et al.  Association of Coronary Wall Shear Stress With Atherosclerotic Plaque Burden, Composition, and Distribution in Patients With Coronary Artery Disease , 2012, Journal of the American Heart Association.

[26]  P. Davies,et al.  Flow-mediated endothelial mechanotransduction. , 1995, Physiological reviews.

[27]  F. Grosveld,et al.  Atherosclerotic Lesion Size and Vulnerability Are Determined by Patterns of Fluid Shear Stress , 2006, Circulation.

[28]  Frits Mastik,et al.  High shear stress induces a strain increase in human coronary plaques over a 6-month period. , 2011, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[29]  Takafumi Hiro,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. , 2008, Journal of the American College of Cardiology.

[30]  Habib Samady,et al.  Contemporary clinical applications of coronary intravascular ultrasound. , 2011, JACC. Cardiovascular interventions.

[31]  R. Virmani,et al.  Concept of vulnerable/unstable plaque. , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[32]  P. Serruys,et al.  The role of shear stress in the destabilization of vulnerable plaques and related therapeutic implications , 2005, Nature Clinical Practice Cardiovascular Medicine.

[33]  W. R. Taylor,et al.  Hemodynamic Shear Stresses in Mouse Aortas: Implications for Atherogenesis , 2006, Arteriosclerosis, thrombosis, and vascular biology.