Published online before print September 23, 2002, doi: 10.1161/01.CIR.0000033220.97592.9A
(Circulation. 2002;106:1962.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Plasma von Willebrand Factor and Soluble P-Selectin as Indices of Endothelial Damage and Platelet Activation in 1321 Patients With Nonvalvular Atrial Fibrillation
Relationship to Stroke Risk Factors
From the Haemostasis Thrombosis and Vascular Biology Unit (D.S.G.C., B.S.P.C., G.Y.H.L.), University Department of Medicine, City Hospital, Birmingham, England; Axio Research Corporation (L.A.P.), Seattle, Wash; and University of Texas Health Science Center (R.G.H.), San Antonio, Tex.
Correspondence to Professor G.Y.H. Lip, University Department of Medicine, City Hospital, Birmingham B18 7QH, England. E-mail g.y.h.lip{at}bham.ac.uk
Background— Epidemiological studies have identified clinical and echocardiographic factors associated with increased stroke risk in atrial fibrillation (AF), but mechanisms linking these factors to stroke in AF are incompletely understood. We hypothesized that stroke risk factors may be associated with increased endothelial damage/dysfunction and platelet activation among patients with AF.
Methods and Results— We measured plasma levels of von Willebrand factor (vWF, a marker of endothelial damage/dysfunction) and soluble P-selectin (sP-sel, a marker of platelet activation) by ELISA in 1321 participants in the Stroke Prevention in Atrial Fibrillation (SPAF) III study and related these indices to the presence of stroke risk factors and cardiovascular disease. Age (P<0.001), prior cerebral ischemia (P<0.01), recent heart failure (P<0.001), diabetes (P<0.001), and body mass index (P<0.001) were independently associated with increased vWF (r2 adjusted=9%). Independent associates of increased sP-sel were diabetes (P=0.01), peripheral vascular disease (P<0.001), and current smoking (P=0.01), whereas prior cerebral ischemia (P=0.002) and female sex (P<0.001) were associated with reduced sP-sel (r2 adjusted=4%). Using prospectively validated stroke risk stratification criteria, we observed a significant stepwise increase in vWF from low- to moderate- to high-risk groups (r2 adjusted=3%, P<0.001), whereas sP-sel remained constant (P= 0.24).
Conclusions— Four recognized risk factors for stroke in AF (advancing age, prior cerebral ischemia, recent heart failure, and diabetes) were independently associated with raised plasma vWF (or endothelial damage/dysfunction), whereas only 1 (diabetes) was associated with increased sP-sel (platelet activation). Further longitudinal studies are now needed to confirm relationships between endothelial damage/dysfunction, platelet activation, and stroke in AF.
Key Words: von Willebrand factor • soluble P-selectin • stroke • risk factors • fibrillation, atrial
This article has been cited by other articles:
 |
|
 |
|
  U. Kalyoncu, O. Dizdar, A. Erkan Duman, O. Karadag, A. Tufan, O. Yucel, O. Tayfur, D. Sen, Z. Ulger, A. Kepez, et al. Alterations of von Willebrand Factor and Ristocetin Cofactor Activity During Atrial Fibrillation Clinical and Applied Thrombosis/Hemostasis, February 1, 2009; 15(1): 103 - 108. [Abstract] [PDF]
|
|
|
|
 |
|
 D. E. Singer, G. W. Albers, J. E. Dalen, M. C. Fang, A. S. Go, J. L. Halperin, G. Y. H. Lip, and W. J. Manning Antithrombotic Therapy in Atrial Fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 546S - 592S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Akar, W. Jeske, and D. J. Wilber Acute Onset Human Atrial Fibrillation Is Associated With Local Cardiac Platelet Activation and Endothelial Dysfunction J. Am. Coll. Cardiol., May 6, 2008; 51(18): 1790 - 1793. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Duygu, V. Barisik, H. Kurt, U. Turk, E. Ercan, and S. Kose Prognostic value of plasma soluble CD40 ligand in patients with chronic non-valvular atrial fibrillation Europace, February 1, 2008; 10(2): 210 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Choudhury, B. Freestone, J. Patel, and G. Y. H. Lip Relationship of Soluble CD40 Ligand to Vascular Endothelial Growth Factor, Angiopoietins, and Tissue Factor in Atrial Fibrillation: A Link Among Platelet Activation, Angiogenesis, and Thrombosis? Chest, December 1, 2007; 132(6): 1913 - 1919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Jaumdally, C. Varma, A. D. Blann, R. J. MacFadyen, and G. Y. H. Lip Platelet Activation in Coronary Artery Disease: Intracardiac vs Peripheral Venous Levels and the Effects of Angioplasty Chest, November 1, 2007; 132(5): 1532 - 1539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Freestone, A. Y. Chong, S. Nuttall, A. D. Blann, and G. Y. H. Lip Soluble E-selectin, von Willebrand Factor, Soluble Thrombomodulin, and Total Body Nitrate/Nitrite Product as Indices of Endothelial Damage/Dysfunction in Paroxysmal, Persistent, and Permanent Atrial Fibrillation Chest, October 1, 2007; 132(4): 1253 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M S O'Neill, A Veves, J A Sarnat, A Zanobetti, D R Gold, P A Economides, E S Horton, and J Schwartz Air pollution and inflammation in type 2 diabetes: a mechanism for susceptibility Occup. Environ. Med., June 1, 2007; 64(6): 373 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Choudhury, I. Chung, A. D. Blann, and G. Y.H. Lip Platelet Surface CD62P and CD63, Mean Platelet Volume, and Soluble/Platelet P-Selectin as Indexes of Platelet Function in Atrial Fibrillation: A Comparison of "Healthy Control Subjects" and "Disease Control Subjects" in Sinus Rhythm J. Am. Coll. Cardiol., May 15, 2007; 49(19): 1957 - 1964. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. I Varughese, J. V Patel, J. Tomson, and G. Y H Lip Effects of blood pressure on the prothrombotic risk in 1235 patients with non-valvular atrial fibrillation Heart, April 1, 2007; 93(4): 495 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Boos, G. Y.H. Lip, and A. D. Blann Circulating Endothelial Cells in Cardiovascular Disease J. Am. Coll. Cardiol., October 17, 2006; 48(8): 1538 - 1547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Writing Committee Members, V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: full text: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Europace, September 1, 2006; 8(9): 651 - 745. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Y.H. Lip, D. Lane, C. Van Walraven, and R. G. Hart Additive Role of Plasma von Willebrand Factor Levels to Clinical Factors for Risk Stratification of Patients With Atrial Fibrillation Stroke, September 1, 2006; 37(9): 2294 - 2300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society J. Am. Coll. Cardiol., August 15, 2006; 48(4): e149 - e246. [Full Text] [PDF]
|
|
|
|
 |
|
 V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society Circulation, August 15, 2006; 114(7): e257 - e354. [Full Text] [PDF]
|
|
|
|
 |
|
 D. Bernhard, A. Csordas, B. Henderson, A. Rossmann, M. Kind, and G. Wick Cigarette smoke metal-catalyzed protein oxidation leads to vascular endothelial cell contraction by depolymerization of microtubules FASEB J, July 1, 2005; 19(9): 1096 - 1107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G Y H Lip, L A Pearce, B S P Chin, D S G Conway, and R G Hart Effects of congestive heart failure on plasma von Willebrand factor and soluble P-selectin concentrations in patients with non-valvar atrial fibrillation Heart, June 1, 2005; 91(6): 759 - 763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Marini, F. De Santis, S. Sacco, T. Russo, L. Olivieri, R. Totaro, and A. Carolei Contribution of Atrial Fibrillation to Incidence and Outcome of Ischemic Stroke: Results From a Population-Based Study Stroke, June 1, 2005; 36(6): 1115 - 1119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Senzaki, C.-H. Chen, H. Ishido, S. Masutani, T. Matsunaga, M. Taketazu, T. Kobayashi, N. Sasaki, S. Kyo, and Y. Yokote Arterial Hemodynamics in Patients After Kawasaki Disease Circulation, April 26, 2005; 111(16): 2119 - 2125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Singer, G. W. Albers, J. E. Dalen, A. S. Go, J. L. Halperin, and W. J. Manning Antithrombotic Therapy in Atrial Fibrillation: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 429S - 456S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. G. Conway, P. Buggins, E. Hughes, and G. Y. H. Lip Relationship of interleukin-6 and C-Reactive protein to the prothrombotic state in chronic atrial fibrillation J. Am. Coll. Cardiol., June 2, 2004; 43(11): 2075 - 2082. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. G. Conway, G. Y. H. Lip, M.-C. Chen, T. Hirai, K. Sakurai, and H. Inoue Further Insights Into the Prothrombotic State in Mitral Stenosis and Atrial Flutter Chest, June 1, 2004; 125(6): 2361 - 2363. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Riediker, W. E. Cascio, T. R. Griggs, M. C. Herbst, P. A. Bromberg, L. Neas, R. W. Williams, and R. B. Devlin Particulate Matter Exposure in Cars Is Associated with Cardiovascular Effects in Healthy Young Men Am. J. Respir. Crit. Care Med., April 15, 2004; 169(8): 934 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Rockson and G. W. Albers Comparing the guidelines: anticoagulation therapy to optimize stroke prevention in patients with atrial fibrillation J. Am. Coll. Cardiol., March 17, 2004; 43(6): 929 - 935. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Blann, S. K. Nadar, and G. Y.H. Lip The adhesion molecule P-selectin and cardiovascular disease Eur. Heart J., December 2, 2003; 24(24): 2166 - 2179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Roldan, F. Marin, A. D Blann, A. Garcia, P. Marco, F. Sogorb, and G. Y.H Lip Interleukin-6, endothelial activation and thrombogenesis in chronic atrial fibrillation Eur. Heart J., July 2, 2003; 24(14): 1373 - 1380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S.G. Conway, L. A. Pearce, B. S.P. Chin, R. G. Hart, and G. Y.H. Lip Prognostic Value of Plasma von Willebrand Factor and Soluble P-Selectin as Indices of Endothelial Damage and Platelet Activation in 994 Patients With Nonvalvular Atrial Fibrillation Circulation, July 1, 2003; 107(25): 3141 - 3145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. G. Hart, J. L. Halperin, L. A. Pearce, D. C. Anderson, R. A. Kronmal, R. McBride, E. Nasco, D. G. Sherman, R. L. Talbert, J. R. Marler, et al. Lessons from the Stroke Prevention in Atrial Fibrillation Trials Ann Intern Med, May 20, 2003; 138(10): 831 - 838. [Abstract] [Full Text] [PDF]
|
|