Subscribe to RSS
DOI: 10.1055/s-0038-1649852
Correlation of Specific Platelet Activation Markers with Carotid Arterial Wall Thickness
Publication History
Received 26 September 1994
Accepted after resubmission 20 April 1995
Publication Date:
09 July 2018 (online)
Summary
Many studies have shown inereased platelet activation in patients with coronary artery, cerebrovascular and peripheral vascular diseases. However, the temporal relationship between platelet activation and arterial atherosclerosis is unclear. To answer this basic question, we measured the plasma concentrations of two specific platelet activation markers, β-thromboglobulin (βTG) and platelet factor 4 (PF4) in 459 cases with increased carotid arterial wall thickness and 459 age-, sex- and race-matched controls selected from a cohort of 15,800 men and women, aged 45-64 who participated in the Atherosclerosis Risk in Communities Study. These participants had no acute vascular symptoms or known cardiovascular disease. The mean values of βTG and PF4 were significantly higher in cases than in controls. However, when analyzed by quartiles using conditional logistic regression, only βTG exhibited a significant association with carotid wall thickness, while PF4 did not. The odds ratio (OR) determined by multivariate logistic regression analysis was significantly higher for the uppermost quartile of βTG (OR=1.7, 95% Cl 1.1-2.5) compared to the lower 3 quartiles. This OR was 2.3 in white men (95% Cl 1.2-4.2), 1.4 in white women (95% Cl 0.6-3.0) and 1.0 in blacks (95% Cl 0.4-2.5).
This study indicates that plasma βTG may be useful as a marker for early atherosclerosis in middle aged adults, particularly in white men. It also suggests that platelet activation has an independent role in the pathogenesis of atherosclerosis, although the possibility that this may be a response to carotid atherosclerosis cannot be excluded.
-
References
- 1 Abrams CS, Ellison AN, Budzinski AZ, Shattil SJ. Direct detection of activated platelets and platelet-derived microparticles in humans. Blood 1990; 75: 128-138
- 2 Ault KA, Kinder HM, Mitchell JG, Kinder CS, Lambrew CT, Hillman RS. Correlated measurement of platelet release and aggregation in whole blood. Cytometry 1989; 10: 445-448
- 3 Galt SW, McDaniel MD, Ault KA, Mitchell J, Cronewett JL. Flow cytometric assessment of platelet function in patients with peripheral arterial occlusive disease. J Vascular Surg 1991; 14: 747-756
- 4 Vreeken J, van Aken WG. Spontaneous aggregation of blood platelets asa cause of idiopathic thrombosis and recurrent painful toes and fingers. Lancet 1971; 2: 1394-1397
- 5 Wu KK, Hoak JC. A new method for the quantitative detection of platelet aggregates in patients with arterial insufficiency. Lancet 1974; 2: 924-926
- 6 Wu KK, Hoak JC. Spontaneous platelet aggregation in arterial insufficiency mechanisms and implication. Thromb Haemost 1976; 35: 702-711
- 7 Steward ME, Douglas JT, Lowe GD O, Prentice CR M, Forbes CD. Prognostic value of β-TG in patients with TIA. Lancet 1983; 2: 749-781
- 8 Preston FE, Ward JD, Marcola BH, Porter NR, Timperly WR, O’Mally BC. Elevated βTG and circulating platelet aggregates in diabetic microangiopathy. Lancet 1978; 1: 238-240
- 9 FitzGerald DJ, Roy L, Catella F, FitzGerald GA. Platelet activation in unstable coronary disease. New Eng J Med 1986; 315: 983-989
- 10 Reilly I AG, Doran JB, Smith B, FitzGerald GA. Increased thromboxane biosynthesis in a human preparation of platelet activation: biochemical and functional consequences of selective inhibition of thromboxane synthase. Circulation 1986; 73: 1300-1309
- 11 Heiss G, Sharrett AR, Barnes R, Chambless LE, Szklo M, Alzola C. And the ARIC Investigators. Carotid atherosclerosis measured by B-mode ultrasound in populations: Associations with cardiovascular risk factors in the ARIC study. Am J Epidemiol 1991; 134: 250-256
- 12 Poli A, Tremoli E, Colombo A, Sirtori M, Pignoli P, Paoletti R. Ultrasonographic measurement of the common carotid artery wall thickness in hyper- cholesterolemic patients. A new model for the quantification and follow-up of preclinical atherosclerosis in living human subjects Atherosclerosis 1988; 70: 253-261
- 13 The ARIC Investigators. The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. Am J Epidemiol. 1989; 129: 687-702
- 14 Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Intimal plus medial thickness of arterial wall: a direct measurement with ultrasound imaging. Circulation 1986; 74: 1399-1406
- 15 National Heart, Lung, and Blood Institute. Atherosclerosis Risk in Communities (ARIC) Study. Operations manual, no. 6A: ultrasound scanning methods. Version 1.0. Chapel Hill, NC: ARIC Coordinating Center. School of Public Health; University of North Carolina: 1987
- 16 National Heart, Lung, and Blood Institute. Atherosclerosis Risk in Communities (ARIC) Study. Operations manual, no. 6B: ultrasound reading methods. Version 1.0 Chapel Hill, NC: ARIC Coordinating Center. School of Public Health; University of North Carolina: 1987
- 17 Bond MG, Barnes RW, Riley WA, Wilmoth SK, Chambless LE, Howard G. Owens B for the ARIC Study Group: High resolution B-mode ultrasound scanning methods in the Atherosclerosis Risk in Communities (ARIC) Study. J Neuroimag. 1991. 1 68-173
- 18 Riley WA, Barnes RW, Bond MG, Evans GW, Chambless LE. Heiss G for the ARIC Study Group: High resolution B-mode ultrasound reading methods in the Atherosclerosis Risk Communities (ARIC) cohort. J Neuroimag 1991; 1: 168-172
- 19 Papp AC, Hatzakis H, Bracey A, Wu KK. ARIC Hemostasis Study-I Development of blood collection and processing systems suitable for multicenter hemostatic studies. Thromb Haemost 1989; 61: 15-19
- 20 Wu KK, Papp AC, Patsch W, Rock R, Eckfeldt J, Sharrett AR. ARIC Hemostasis Study-II Organizational plan and feasibility study. Thromb Haemost 1990; 64: 521-525
- 21 Kaplan KL. β-Thromboglobulin. Prog Hemost Thromb 1980; 5: 153-178
- 22 National Heart, Lung, and Blood Institute. ARIC manual of procedure No. 9. Hemostasis Determination, Chapel Hill, NC: ARIC Coordinating Center. School of Public Health; University of North Carolina: 1987
- 23 National Heart, Lung and Blood Institute. ARIC Manual of Procedure no. 8. Lipid and Lipoprotein determinations. Chapel Hill NC: ARIC Coordinating Center. School of Public Health. University of North Carolina: 1987
- 24 Nguyen ND, Ghaddar HM, Stinson V, Chambless LE, Wu KK. ARIC Hemostasis Study-IV. Intraindividual variability and reliability coefficient of hemostatic factors. submitted; 1994
- 25 SAS User’s Guide: Statistics. Cary, NS: SAS Institute. 1985
- 26 Salonen JT, Seppanen K, Rauramaa R, Salonen JT. Prevalence of carotid atherosclerosis and serum cholesterol levels in Eastern Finland. Arteriosclerosis 1988; 8: 788-792
- 27 Salonen R, Salonen J. Progression of carotid atherosclerosis and its determinants: a population-based ultrasonography study. Atherosclerosis 1990; 81: 33-40
- 28 Born GVR. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962; 194: 927-929
- 29 FitzGerald GA, Pedersen AK, Patrono C. Analysis of prostacyclin and thromboxane biosynthesis in cardiovascular disease. Circulation 1983; 67: 1174-1177
- 30 Shattil SJ, Cunningham M, Hoxie JA. Detection of activated platelets in whole blood using activation-dependent monoclonal antibodies and flow cytometry. Blood 1987; 70: 307-315
- 31 Shah AB, Beamer N, Coull BM. Enhanced in vivo platelet activation in subtypes of ischemic stroke. Stroke 1985; 16: 643-647
- 32 Mathis PC, Wohl H, Wallach SR, Engler RZ. Lack of release of platelet factor 4 during exercise induced myocardial ischemia. New Eng J Med 1981; 304: 1275-1278
- 33 FitzGerald DJ, Roy L, Catella F, FitzGerald GA. Platelet activation in unstable coronary disease. New Eng J Med 1986; 315: 983-989
- 34 Smitherman TC, Milam M, Woo J, Willerson J, Frenkel EP. Elevated β-thromboglobulin in peripheral venous blood of patients with acute myocardial ischemia: direct evidence for enhanced platelet reactivity in vivo. Amer J Cardiol 1981; 48: 395-401
- 35 Rasi V, Ikkala E, Torstila I. Plasma β-thromboglobulin in acute myocardial infarction. Thromb Res 1982; 25: 203-212
- 36 Levine SP, Lindenfeld J, Ellis B, Raymond NM, Krentz LS. Increased plasma concentrations of platelet factor 4 in coronary artery disease. Circulation 1981; 64: 626-632
- 37 Handin RI, McDonough M, Lesch M. Elevation of platelet factor four in acute myocardial infarction: measurement by radioimmunoassay. J Lab Clin Med 1978; 91: 340-349
- 38 White GC, Marouf AA. Platelet factor 4 in patients with coronary artery disease. J Lab Clin Med 1981; 97: 369-378
- 39 Green LH, Seroppian E, Handin RI. Platelet activation during exercise-induced myocardial ischemia. New Eng J Med 1980; 302: 193-197
- 40 Hirsch PD, Hillis LD, Campbell WB, Firth BG, Willerson JT. Release of prostaglandins and thromboxane into coronary circulation in patients with ischemic heart disease. New Eng J Med 1981; 304: 685-691
- 41 Mehta P, Mehta J. Platelet function studies in coronary artery disease. V. Evidence for enhanced platelet microthrombus formation activity in acute myocardial infarction. Am J Cardiol 1979; 43: 757-760
- 42 Wu KK, Hoak JC. Increased platelet aggregates in patients with transient ischemic attacks. Stroke 1975; 6: 521-524
- 43 Dougherty Jr JH, Levy DE, Weksler BB. Platelet activation in acute cerebral ischemia. Lancet 1977; 1: 821-824
- 44 Stewart ME, Douglas JT, Lowe GD O, Prentice CR M, Forbes CD. Prognostic value of β-thromboglobulin in patients with transient cerebral ischemia. Lancet 1983; 2: 479-482
- 45 Uchiyama S, Takeuchi N, Osawa M, Kobayashi I, Murayama S, Aosaki M, Hirosawa K. Platelet function tests in thrombotic cerebrovascular disorders. Stroke 1983; 14: 511-517
- 46 Celia G, Zahavi J, DeHass HA, Kakkar VV. β-thromboglobulin, platelet production time and platelet function in vascular disease. Brit J Haematol 1979; 43: 127-136
- 47 Persson J, Formgren J, Israelsson B, Berglund B. Ultrasound-determined intima-media thickness and atherosclerosis. Direct and indirect validation. Arterioscler Thromb 1994; 14: 261-264
- 48 Trip MD, Cats VM, vanCapelle FJ L, Vreeken J. Platelet hyperactivity and prognosis in survivors of myocardial infarction. New Eng J Med 1990; 323: 1549-1554