(Circulation. 1997;96:69-75.)
© 1997 American Heart Association, Inc.
Articles |
Diabetes Mellitus, Hypercholesterolemia, and Hypertension but Not Vascular Disease Per Se Are Associated With Persistent Platelet Activation In Vivo
Evidence Derived From the Study of Peripheral Arterial Disease
From the Departments of Medicine (G.D., C.G.) and Pharmacology (C.P.), University of Chieti "G. D'Annunzio"; the Institute of Internal and Vascular Medicine (P.G., R.V., G.G.N.), University of Perugia; Department of Medicine (F.V., S.B.), University of Rome; the Research Center of Vascular Diseases (M.C.), University of Milan; and Department of Pharmacology (G.C.), Catholic University of Rome, Italy.
Correspondence to Prof Carlo Patrono, Cattedra di Farmacologia I, Università degli Studi "G. D'Annunzio," Via dei Vestini, 31, 66013 Chieti, Italy. E-mail cpatrono{at}unich.it
Background Previous studies relating increased thromboxane (TX) biosynthesis to cardiovascular risk factors do not answer the question whether platelet activation is merely a consequence of more prevalent atherosclerotic lesions or reflects the influence of metabolic and hemodynamic disturbances on platelet biochemistry and function.
Methods and Results We examined 64 patients with large-vessel peripheral arterial disease and 64 age- and sex-matched control subjects. TXA2 biosynthesis was investigated in relation to cardiovascular risk factors by repeated measurements of the urinary excretion of its major enzymatic metabolite, 11-dehydro-TXB2, by radioimmunoassay. Urinary 11-dehydro-TXB2 was significantly (P=.0001) higher in patients with peripheral arterial disease (57±26 ng/h) than in control subjects (26±7 ng/h). Seventy percent of patients had metabolite excretion >2 SD above the normal mean. However, 11-dehydro-TXB2 excretion was enhanced only in association with cardiovascular risk factors. Multivariate analysis showed that diabetes, hypercholesterolemia, and hypertension were independently related to 11-dehydro-TXB2 excretion. During a median follow-up of 48 months, 8 patients experienced major vascular events. These patients had significantly (P=.001) higher 11-dehydro-TXB2 excretion at baseline than patients who remained event free.
Conclusions The occurrence of large-vessel peripheral arterial disease per se is not a trigger of platelet activation in vivo. Rather, the rate of TXA2 biosynthesis appears to reflect the influence of coexisting disorders such as diabetes mellitus, hypercholesterolemia, and hypertension on platelet biochemistry and function. Enhanced TXA2 biosynthesis may represent a common link between such diverse risk factors and the thrombotic complications of peripheral arterial disease.
Key Words: peripheral vascular disease • thromboxane • diabetes mellitus • hypercholesterolemia • hypertension
This article has been cited by other articles:
 |
|
 |
|
  N. Zimmermann, E. Gams, and T. Hohlfeld Aspirin in coronary artery bypass surgery: new aspects of and alternatives for an old antithrombotic agent. Eur. J. Cardiothorac. Surg., July 1, 2008; 34(1): 93 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Davi and C. Patrono Platelet Activation and Atherothrombosis N. Engl. J. Med., December 13, 2007; 357(24): 2482 - 2494. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Migliacci, C. Becattini, R. Pesavento, G. Davi, M. C. Vedovati, G. Guglielmini, E. Falcinelli, G. Ciabattoni, F. Dalla Valle, P. Prandoni, et al. Endothelial dysfunction in patients with spontaneous venous thromboembolism Haematologica, June 1, 2007; 92(6): 812 - 818. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Angulo, P. Cuevas, A. Fernandez, A. Allona, I. Moncada, A. Martin-Morales, J. M. La Fuente, and I. S. de Tejada Enhanced Thromboxane Receptor-Mediated Responses and Impaired Endothelium-Dependent Relaxation in Human Corpus Cavernosum from Diabetic Impotent Men: Role of Protein Kinase C Activity J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 783 - 789. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. F. Slaughter Hemostasis and glycemic control in the cardiac surgical patient. Seminars in Cardiothoracic and Vascular Anesthesia, June 1, 2006; 10(2): 176 - 179. [Abstract] [PDF]
|
|
|
|
 |
|
 H. -K. Yip, C. -H. Lu, C. -H. Yang, H. -W. Chang, W. -C. Hung, C. -I. Cheng, S. -M. Chen, and C. -J. Wu Levels and value of platelet activity in patients with severe internal carotid artery stenosis Neurology, March 28, 2006; 66(6): 804 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Morrow Quantification of Isoprostanes as Indices of Oxidant Stress and the Risk of Atherosclerosis in Humans Arterioscler. Thromb. Vasc. Biol., February 1, 2005; 25(2): 279 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. L. Hall, Y. M. Jeanes, and J. K. Lodge Hyperlipidemic Subjects Have Reduced Uptake of Newly Absorbed Vitamin E into Their Plasma Lipoproteins, Erythrocytes, Platelets, and Lymphocytes, as Studied by Deuterium-Labeled {alpha}-Tocopherol Biokinetics J. Nutr., January 1, 2005; 135(1): 58 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Gresele and R. Migliacci Picotamide versus aspirin in diabetic patients with peripheral arterial disease: has David defeated Goliath? Eur. Heart J., October 2, 2004; 25(20): 1769 - 1771. [Full Text] [PDF]
|
|
|
|
|
|
A. Schafer, N. J. Alp, S. Cai, C. A. Lygate, S. Neubauer, M. Eigenthaler, J. Bauersachs, and K. M. Channon Reduced Vascular NO Bioavailability in Diabetes Increases Platelet Activation In Vivo Arterioscler. Thromb. Vasc. Biol., September 1, 2004; 24(9): 1720 - 1726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Valgimigli, G. Percoco, D. Barbieri, F. Ferrari, G. Guardigli, G. Parrinello, O. Soukhomovskaia, and R. Ferrari The additive value of tirofiban administered with the high-dose bolus in the prevention of ischemic complications during high-risk coronary angioplasty: The advance trial J. Am. Coll. Cardiol., July 7, 2004; 44(1): 14 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-K. Yip, S.-S. Chen, J. S. Liu, H.-W. Chang, Y.-F. Kao, M.-Y. Lan, Y.-Y. Chang, S.-L. Lai, W.-H. Chen, and M.-C. Chen Serial Changes in Platelet Activation in Patients After Ischemic Stroke: Role of Pharmacodynamic Modulation Stroke, July 1, 2004; 35(7): 1683 - 1687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bruno, J. P. McConnell, S. N. Cohen, G. E. Tietjen, R. A. Wallis, P. B. Gorelick, and N. U. Bang Serial Urinary 11-Dehydrothromboxane B2, Aspirin Dose, and Vascular Events in Blacks After Recent Cerebral Infarction Stroke, March 1, 2004; 35(3): 727 - 730. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Minuz, P. Patrignani, S. Gaino, F. Seta, M. L. Capone, S. Tacconelli, M. Degan, G. Faccini, A. Fornasiero, G. Talamini, et al. Determinants of Platelet Activation in Human Essential Hypertension Hypertension, January 1, 2004; 43(1): 64 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Gresele, G. Guglielmini, M. De Angelis, S. Ciferri, M. Ciofetta, E. Falcinelli, C. Lalli, G. Ciabattoni, G. Davi, and G. B. Bolli Acute, short-term hyperglycemia enhances shear stress-induced platelet activation in patients with type II diabetes mellitus J. Am. Coll. Cardiol., March 19, 2003; 41(6): 1013 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Preston, W. Jy, J. J. Jimenez, L. M. Mauro, L. L. Horstman, M. Valle, G. Aime, and Y. S. Ahn Effects of Severe Hypertension on Endothelial and Platelet Microparticles Hypertension, February 1, 2003; 41(2): 211 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Quinn, E. F. Plow, and E. J. Topol Platelet Glycoprotein IIb/IIIa Inhibitors: Recognition of a Two-Edged Sword? Circulation, July 16, 2002; 106(3): 379 - 385. [Full Text] [PDF]
|
|
|
|
|
|
M. Roffi, D. J. Moliterno, B. Meier, E. R. Powers, C. L. Grines, P. M. DiBattiste, H. C. Herrmann, M. Bertrand, K. E. Harris, L. A. Demopoulos, et al. Impact of Different Platelet Glycoprotein IIb/IIIa Receptor Inhibitors Among Diabetic Patients Undergoing Percutaneous Coronary Intervention: Do Tirofiban and ReoPro Give Similar Efficacy Outcomes Trial (TARGET) 1-Year Follow-Up Circulation, June 11, 2002; 105(23): 2730 - 2736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. H. Smith, O. Boutaud, M. Breyer, J. D. Morrow, J. A. Oates, and D. E. Vaughan Cyclooxygenase-2-Dependent Prostacyclin Formation Is Regulated by Low Density Lipoprotein Cholesterol In Vitro Arterioscler. Thromb. Vasc. Biol., June 1, 2002; 22(6): 983 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Roffi, D. P. Chew, D. Mukherjee, D. L. Bhatt, J. A. White, C. Heeschen, C. W. Hamm, D. J. Moliterno, R. M. Califf, H. D. White, et al. Platelet Glycoprotein IIb/IIIa Inhibitors Reduce Mortality in Diabetic Patients With Non-ST-Segment-Elevation Acute Coronary Syndromes Circulation, December 4, 2001; 104(23): 2767 - 2771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Garlichs, S. John, A. Schmei{beta}er, S. Eskafi, C. Stumpf, M. Karl, M. Goppelt-Struebe, R. Schmieder, and W. G. Daniel Upregulation of CD40 and CD40 Ligand (CD154) in Patients With Moderate Hypercholesterolemia Circulation, November 13, 2001; 104(20): 2395 - 2400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Pratico, T. Cyrus, H. Li, and G. A. FitzGerald Endogenous biosynthesis of thromboxane and prostacyclin in 2 distinct murine models of atherosclerosis Blood, December 1, 2000; 96(12): 3823 - 3826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Theroux, J. Alexander Jr, C. Pharand, E. Barr, S. Snapinn, A. F. Ghannam, and F. L. Sax Glycoprotein IIb/IIIa Receptor Blockade Improves Outcomes in Diabetic Patients Presenting With Unstable Angina/Non-ST-Elevation Myocardial Infarction : Results From the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Circulation, November 14, 2000; 102(20): 2466 - 2472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Izrailtyan, J. Y. Kresh, R. J. Morris, S. C. Brozena, S. P. Kutalek, and A. S. Wechsler Early detection of acute allograft rejection by linear and nonlinear analysis of heart rate variability J. Thorac. Cardiovasc. Surg., October 1, 2000; 120(4): 737 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schwemmer, O. Sommer, R. Koeckerbauer, and E. Bassenge Cardiovascular Dysfunction in Hypercholesterolemia Associated With Enhanced Formation of ATI-Receptor and of Eicosanoids Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2000; 5(1): 59 - 68. [Abstract] [PDF]
|
|
|
|
 |
|
 N. M Smith, R. Pathansali, and P. M. Bath Platelets and stroke Vascular Medicine, August 1, 1999; 4(3): 165 - 172. [Abstract] [PDF]
|
|
|
|
|
|
F. van Kooten, G. Ciabattoni, P. J. Koudstaal, D. E. Grobbee, C. Kluft, and C. Patrono Increased Thromboxane Biosynthesis Is Associated With Poststroke Dementia Stroke, August 1, 1999; 30(8): 1542 - 1547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. van Kooten, G. Ciabattoni, P. J. Koudstaal, D. W. J. Dippel, and C. Patrono Increased Platelet Activation in the Chronic Phase After Cerebral Ischemia and Intracerebral Hemorrhage Stroke, March 1, 1999; 30(3): 546 - 549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Davi, G. Ciabattoni, A. Consoli, A. Mezzetti, A. Falco, S. Santarone, E. Pennese, E. Vitacolonna, T. Bucciarelli, F. Costantini, et al. In Vivo Formation of 8-Iso-Prostaglandin F2{alpha} and Platelet Activation in Diabetes Mellitus : Effects of Improved Metabolic Control and Vitamin E Supplementation Circulation, January 19, 1999; 99(2): 224 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gawaz, F.-J. Neumann, and A. Schomig Evaluation of Platelet Membrane Glycoproteins in Coronary Artery Disease : Consequences for Diagnosis and Therapy Circulation, January 12, 1999; 99 (1): e1 - e11. [Full Text] [PDF]
|
|