Von Willebrand factor in relation to coronary plaque characteristics and cardiovascular outcome

Summary High von Willebrand factor (VWF) plasma levels are associated with an increased risk of coronary artery disease. It has been suggested that the increase of VWF levels is partly due to endothelial dysfunction and atherosclerosis. Our aim was to investigate the association between coronary plaque burden, the presence of high-risk coronary lesions as measured by intravascular ultrasound virtual histology (IVUS-VH) and VWF levels. In addition, we studied the association between VWF levels and one-year cardiovascular outcome. Between 2008 and 2011, IVUS-VH imaging of a non-culprit coronary artery was performed in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS) (n= 318) or stable angina pectoris (SAP) (n= 263). Arterial blood was sampled prior to the coronary angiography. VWF antigen (VWF:Ag) levels were measured using ELISA (n= 577). Patients with ACS had significantly higher VWF:Ag levels than SAP patients (median 1.73 IU/ml [IQR 1.27–2.31] vs 1.26 IU/ml [0.93–1.63], p < 0.001). High coronary plaque burden was associated with higher VWF:Ag levels (β= 0.12, p=0.027) in SAP patients, but not in ACS patients. In ACS patients, VWF:Ag levels were associated with 1-year MACE (HR 4.14 per SD increase of lnVWF:Ag, 95 % CI 1.47–11.6), whereas in SAP patients VWF:Ag levels predicted 1-year all-cause death and hospitalisation for ACS (HR 7.07 95 % CI 1.40–35.6). In conclusion, coronary plaque burden was associated with VWF:Ag levels in SAP patients undergoing coronary angiography. In ACS and SAP patients, high VWF levels are predictive of adverse cardiovascular outcome and death during one-year follow-up.

[1]  Jeroen J. Bax,et al.  2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). , 2011, European heart journal.

[2]  G. Vanhoutte,et al.  Elastin fragmentation in atherosclerotic mice leads to intraplaque neovascularization, plaque rupture, myocardial infarction, stroke, and sudden death , 2014, European heart journal.

[3]  F. Leebeek,et al.  Von Willebrand factor and ADAMTS13 in arterial thrombosis: a systematic review and meta-analysis. , 2014, Blood reviews.

[4]  Evelyn Regar,et al.  In vivo detection of high-risk coronary plaques by radiofrequency intravascular ultrasound and cardiovascular outcome: results of the ATHEROREMO-IVUS study. , 2014, European heart journal.

[5]  E. Halperin,et al.  Relation of genetic profile and novel circulating biomarkers with coronary plaque phenotype as determined by intravascular ultrasound: rationale and design of the ATHEROREMO-IVUS study. , 2014, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[6]  P. Moreno.  Prediction of MACE after ACS: demographics and angiography versus imaging. , 2013, JACC. Cardiovascular imaging.

[7]  P. Koudstaal,et al.  Relationship of Von Willebrand Factor with carotid artery and aortic arch calcification in ischemic stroke patients. , 2013, Atherosclerosis.

[8]  I. Haviv,et al.  A Novel Mouse Model of Atherosclerotic Plaque Instability for Drug Testing and Mechanistic/Therapeutic Discoveries Using Gene and MicroRNA Expression Profiling , 2013, Circulation research.

[9]  V. Gudnason,et al.  Hemostatic Factors and Risk of Coronary Heart Disease in General Populations: New Prospective Study and Updated Meta-Analyses , 2013, PloS one.

[10]  A. Hofman,et al.  von Willebrand factor plasma levels, genetic variations and coronary heart disease in an older population , 2012, Journal of thrombosis and haemostasis : JTH.

[11]  Jeroen J. Bax,et al.  ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation , 2012 .

[12]  T. Lauer,et al.  Kardiologische Aspekte der präoperativen Risikostratifizierung , 2011 .

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

[14]  Patrick W. Serruys,et al.  Assessment of coronary atherosclerosis by IVUS and IVUS-based imaging modalities: progression and regression studies, tissue composition and beyond , 2011, The International Journal of Cardiovascular Imaging.

[15]  P. Serruys,et al.  IVUS-based imaging modalities for tissue characterization: similarities and differences , 2011, The International Journal of Cardiovascular Imaging.

[16]  Patrick W Serruys,et al.  Imaging of coronary atherosclerosis: intravascular ultrasound. , 2010, European heart journal.

[17]  O. McCarty,et al.  Molecular imaging of activated von Willebrand factor to detect high-risk atherosclerotic phenotype. , 2010, JACC. Cardiovascular imaging.

[18]  P. Whincup,et al.  Circulating inflammatory and hemostatic biomarkers are associated with risk of myocardial infarction and coronary death, but not angina pectoris, in older men , 2009, Journal of thrombosis and haemostasis : JTH.

[19]  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.

[20]  Y Zhang,et al.  Animal models and potential mechanisms of plaque destabilisation and disruption , 2009, Heart.

[21]  A. Bertomoro,et al.  Type IIB von Willebrand Disease: Role of Qualitative Defects in Atherosclerosis and Endothelial Dysfunction , 2007, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[22]  G. Lowe,et al.  Relative Value of Inflammatory, Hemostatic, and Rheological Factors for Incident Myocardial Infarction and Stroke: The Edinburgh Artery Study , 2007, Circulation.

[23]  Erling Falk,et al.  Plaque rupture in humans and mice. , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[24]  Z. Ruggeri,et al.  The role of von Willebrand factor in thrombus formation. , 2007, Thrombosis research.

[25]  U. Vischer,et al.  von Willebrand factor, endothelial dysfunction, and cardiovascular disease , 2006, Journal of thrombosis and haemostasis : JTH.

[26]  W. März,et al.  Markers for endothelial dysfunction, but not markers for oxidative stress correlate with classical risk factors and the severity of coronary artery disease , 2006, Scandinavian cardiovascular journal : SCJ.

[27]  Marco Valgimigli,et al.  In vivo intravascular ultrasound-derived thin-cap fibroatheroma detection using ultrasound radiofrequency data analysis. , 2005, Journal of the American College of Cardiology.

[28]  Renu Virmani,et al.  Pathology of the thin-cap fibroatheroma: a type of vulnerable plaque. , 2003, Journal of interventional cardiology.

[29]  J. Danesh,et al.  von Willebrand factor and coronary heart disease: prospective study and meta-analysis. , 2002, European heart journal.

[30]  D. Wagner,et al.  Localized reduction of atherosclerosis in von Willebrand factor-deficient mice. , 2001, Blood.

[31]  J. Reiber,et al.  Decreased Coagulability Has No Clinically Relevant Effect on Atherogenesis: Observations in Individuals With a Hereditary Bleeding Tendency , 2001, Circulation.

[32]  A. Folsom,et al.  Prospective study of markers of hemostatic function with risk of ischemic stroke. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. , 1999, Circulation.

[33]  K. Williams,et al.  Atherosclerosis--an inflammatory disease. , 1999, The New England journal of medicine.

[34]  G. Lowe,et al.  Factor VIII, von Willebrand factor and the risk of major ischaemic heart disease in the Caerphilly Heart Study , 1999, British journal of haematology.

[35]  A. Blann,et al.  Von Willebrand factor, P-selectin and fibrinogen levels in patients with acute ischaemic and haemorrhagic stroke, and their relationship with stroke sub-type and functional outcome. , 1998, Platelets.

[36]  J. Barrett,et al.  von Willebrand Factor and Factor VIII: C in Acute Cerebrovascular Disease , 1997, Thrombosis and Haemostasis.

[37]  G. Lip,et al.  von Willebrand factor: a marker of endothelial dysfunction in vascular disorders? , 1997, Cardiovascular research.

[38]  A. Folsom,et al.  Association of hemostatic variables with prevalent cardiovascular disease and asymptomatic carotid artery atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[39]  A. Federici,et al.  Autopsy Findings in Three Patients with von Willebrand Disease Type IIB and Type III: Presence of Atherosclerotic Lesions without Occlusive Arterial Thrombi , 1993, Thrombosis and Haemostasis.

[40]  J. Jansson,et al.  von Willebrand factor in plasma: a novel risk factor for recurrent myocardial infarction and death , 1992, British heart journal.

[41]  J. Pearson,et al.  von Willebrand factor is an acute phase reactant in man. , 1989, Thrombosis research.

[42]  V. Fuster,et al.  Arteriosclerosis in Normal and von Willebrand Pigs: Long‐Term Prospective Study and Aortic Transplantation Study , 1982, Circulation research.

[43]  V. Fuster,et al.  Resistance to arteriosclerosis in pigs with von Willebrand's disease. Spontaneous and high cholesterol diet-induced arteriosclerosis. , 1978, The Journal of clinical investigation.